<PAGE>

     As filed with the Securities and Exchange Commission on August 06, 1999
                                                           Registration No. 333-

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                             ----------------------

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                              --------------------


                              Gilead Sciences, Inc.
                              ---------------------
             (Exact name of registrant as specified in its charter)
                                 -------------

              Delaware                                94-3047598                
       --------------------              ---------------------------------
     (State of Incorporation)           (I.R.S. Employer Identification No.)


                                 --------------

                               333 Lakeside Drive
                              Foster City, CA 94404
                 ---------------------------------------------
                    (Address of principal executive offices)

                                  -------------



                             1991 Stock Option Plan
                 1995 Non-Employee Directors' Stock Option Plan
                          Employee Stock Purchase Plan
                 ----------------------------------------------
                            (Full title of the plans)


                               Mark L. Perry, Esq.
       Senior Vice President, Chief Financial Officer and General Counsel
                              Gilead Sciences, Inc.
                               333 Lakeside Drive
                              Foster City, CA 94404
                                 (650) 574-3000
                   -------------------------------------------
       (Name, address, including zip code, and telephone number, including
                        area code, of agent for service)


                               -----------------

                                   Copies to:
                             Julia L. Davidson, Esq.
                               Cooley Godward llp
                              Five Palo Alto Square
                               3000 El Camino Real
                               Palo Alto, CA 94306
                                 (650) 843-5000
                               ------------------


<PAGE>

                         CALCULATION OF REGISTRATION FEE

<TABLE>
<CAPTION>

========================== ====================== ========================= ========================== =========================
                                                      PROPOSED MAXIMUM          PROPOSED MAXIMUM
 TITLE OF SECURITIES TO                              OFFERING PRICE PER     AGGREGATE OFFERING PRICE
      BE REGISTERED            AMOUNT TO BE              SHARE (1)                     (1)              AMOUNT OF REGISTRATION
                                REGISTERED                                                                       FEE
-------------------------- ---------------------- ------------------------- -------------------------- -------------------------
<S>                        <C>                    <C>                       <C>                        <C>
Stock Options and 
Common Stock (par                4,030,000                $72.00                $290,160,000.00               $80,664.48
value $.001)
========================== ====================== ========================= ========================== =========================

</TABLE>


(1)      Estimated solely for the purpose of calculating the amount of the
         registration fee pursuant to Rule 457(c). The price per share and
         aggregate offering price are based upon the closing sales price of
         Registrant's Common Stock on August 5, 1999 as reported on the Nasdaq
         National Market.


<PAGE>

                    INCORPORATION BY REFERENCE OF CONTENTS OF
                      REGISTRATION STATEMENTS ON FORMS S-8

         The contents of Registration Statement on Form S-8 No. 33-46058 filed
with the Securities and Exchange Commission on March 3, 1992 is incorporated by
reference herein.

         The contents of Registration Statement on Form S-8 No. 33-62060 filed 
with the Securities and Exchange Commission on May 3, 1993 is incorporated by 
reference herein.

         The contents of Registration Statement on Form S-8 No. 33-81670 filed 
with the Securities and Exchange Commission on July 18, 1994 is incorporated 
by reference herein.

         The contents of Registration Statement on Form S-8 No. 333-08083 filed
with the Securities and Exchange Commission on July 12, 1996 is incorporated by
reference herein.

         The contents of Registration Statement on Form S-8 No. 333-08085 filed
with the Securities and Exchange Commission on July 12, 1996 is incorporated by
reference herein.

         The contents of Registration Statement on Form S-8 No. 333-58893 filed
with the Securities and Exchange Commission on July 10, 1998 is incorporated
by reference herein.

                                 EXHIBITS


<TABLE>
<CAPTION>
EXHIBIT
NUMBER
------
<S>               <C>
         3.1   (1)   Certificate of Amendment to Restated Certificate of Incorporation 
                     of the Registrant

         3.2   (2)   Amended and Restated Certificate of Incorporation of the 
                     Registrant

         3.3   (3)   Bylaws of the Registrant, as amended and restated March 30, 1999

         4.1         Reference is made to Exhibits 3.1, 3.2, and 3.3

         4.2   (4)   Rights Agreement dated as of November 21, 1994, between 
                     Registrant and First Interstate Bank, with exhibits

         4.3   (4)   Form of letter sent to Gilead Sciences, Inc. stockholders, dated 
                     December 14, 1994

         4.4   (1)   First Supplemental Indenture dated July 29, 1999 among IBJ 
                     Whitehall Bank & Trust Company, NeXstar Pharmaceuticals, Inc. and 
                     the Registrant to the Indenture dated July 31, 1997 between IBJ 
                     Whitehall Bank & Trust Company and NeXstar Pharmaceuticals, Inc.

         4.5   (5)   Indenture dated July 31, 1997 between IBJ Whitehall Bank & Trust 
                     Company and NeXstar Pharmaceuticals, Inc. for NeXstar's 6 1/4% 
                     Convertible Subordinated Debentures

         5.1         Opinion of Cooley Godward LLP

         23.1        Consent of Ernst & Young LLP, Independent Auditors

         23.2        Consent of Cooley Godward LLP is contained in Exhibit 5.1 to this
                     Registration Statement

         24.1        Power of Attorney is contained on the signature pages

         99.1  (3)   1991 Stock Option Plan, as amended as of March 30, 1999

         99.2  (3)   Employee Stock Purchase Plan, as amended as of March 30,
                     1999

         99.3  (6)   1995 Non-Employee Director's Stock Option Plan, as amended
                     as of January 26, 1999
</TABLE>


(1)  Filed as an exhibit to Registrant's Current Report on Form 8-K filed on 
     August 6, 1999 and incorporated herein by reference.

(2)  Filed as an exhibit to Registrant's Registration Statement on Form S-8 
     (No. 33-46058) and incorporated herein by reference.

(3)  Filed as an exhibit to Registrant's Annual Report on Form 10-K/A for the 
     fiscal year ended December 31, 1998 and incorporated herein by reference.

(4)  Filed as an exhibit to Registrant's Quarterly Report on Form 10-Q for 
     the quarter ended December 31, 1994 and incorporated herein by reference.

(5)  Filed as an exhibit to NeXstar Pharmaceutical, Inc.'s Quarterly Report 
     on Form 10-Q for the quarter ended June 30, 1997 and incorporated herein 
     by reference.

(6)  Filed as an exhibit to Registrant's Annual Report on Form 10-K for the 
     fiscal year ended December 31, 1998 and incorporated herein by reference.


<PAGE>

                                   SIGNATURES

         Pursuant to the requirements of the Securities Act of 1933, as amended,
the Registrant certifies that it has reasonable grounds to believe that it meets
all of the requirements for filing on Form S-8 and has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of Foster City, State of California, on August 6,
1999.


                                GILEAD SCIENCES, INC.



                                By:    /s/John C. Martin
                                       -----------------
                                       John C. Martin
                                       President and Chief Executive Officer




                                POWER OF ATTORNEY


         KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature
appears below constitutes and appoints John C. Martin and Mark L. Perry, and
each or any one of them, his true and lawful attorney-in-fact and agent, with
full power of substitution and resubstitution, for him and in his name, place
and stead, in any and all capacities, to sign any and all amendments (including
post-effective amendments) to this Registration Statement, and to file the same,
with all exhibits thereto, and other documents in connection therewith, with the
Securities and Exchange Commission, granting unto said attorneys-in-fact and
agents, and each of them, full power and authority to do and perform each and
every act and thing requisite and necessary to be done in connection therewith,
as fully to all intents and purposes as he might or could do in person, hereby
ratifying and confirming all that said attorneys-in-fact and agents, or any of
them, or their or his substitutes or substitute, may lawfully do or cause to be
done by virtue hereof.


<PAGE>

         Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed by the following persons in the
capacities and on the dates indicated.

SIGNATURE                             TITLE                             DATE

<TABLE>
<CAPTION>

<S>                                   <C>                               <C>
/s/ John C. Martin                    President, Chief Executive        August 6 , 1999
---------------------------------     Officer and Director
         John C. Martin




/s/ Mark L. Perry                     Senior Vice President, Chief      August 6 , 1999
---------------------------------     Financial Officer and General
         Mark L. Perry                Counsel



/s/ Paul Berg                         Director                          August 6 , 1999
---------------------------------
         Paul Berg



/s/ Etienne F. Davignon               Director                          August 6 , 1999
---------------------------------
         Etienne F. Davignon



/s/ James M. Denny, Sr.               Director                          August 6 , 1999
---------------------------------
         James M. Denny, Sr.                                                           



/s/ Gordon E. Moore                   Director                          August 6 , 1999
---------------------------------
         Gordon E. Moore                                                               


/s/ Donald H. Rumsfeld                Director                          August 6 , 1999
---------------------------------
         Donald H. Rumsfeld                                                            


/s/ George P. Shultz                  Director                          August 6 , 1999
---------------------------------
         George P. Shultz                                                              
</TABLE>



<PAGE>



                                  EXHIBIT INDEX

<TABLE>
<CAPTION>

         EXHIBIT
         NUMBER                                          DESCRIPTION                                SEQUENTIAL PAGE NUMBER
         <S>                                             <C>                                        <C>

         3.1   (1)   Certificate of Amendment to Restated Certificate of Incorporation 
                     of the Registrant

         3.2   (2)   Amended and Restated Certificate of Incorporation of the 
                     Registrant

         3.3   (3)   Bylaws of the Registrant, as amended and restated March 30, 1999

         4.1         Reference is made to Exhibits 3.1, 3.2, and 3.3

         4.2   (4)   Rights Agreement dated as of November 21, 1994, between 
                     Registrant and First Interstate Bank, with exhibits

         4.3   (4)   Form of letter sent to Gilead Sciences, Inc. stockholders, dated 
                     December 14, 1994

         4.4   (1)   First Supplemental Indenture dated July 29, 1999 among IBJ 
                     Whitehall Bank & Trust Company, NeXstar Pharmaceuticals, Inc. and 
                     the Registrant to the Indenture dated July 31, 1997 between IBJ 
                     Whitehall Bank & Trust Company and NeXstar Pharmaceuticals, Inc.

         4.5   (5)   Indenture dated July 31, 1997 between IBJ Whitehall Bank & Trust 
                     Company and NeXstar Pharmaceuticals, Inc. for NeXstar's 6 1/4% 
                     Convertible Subordinated Debentures

         5.1         Opinion of Cooley Godward LLP

         23.1        Consent of Ernst & Young LLP, Independent Auditors

         23.2        Consent of Cooley Godward LLP is contained in Exhibit 5.1 to this
                     Registration Statement

         24.1        Power of Attorney is contained on the signature pages

         99.1  (3)   1991 Stock Option Plan, as amended as of March 30, 1999

         99.2  (3)   Employee Stock Purchase Plan, as amended as of March 30,
                     1999

         99.3  (6)   1995 Non-Employee Director's Stock Option Plan, as amended
                     as of January 26, 1999
</TABLE>


(1)  Filed as an exhibit to Registrant's Current Report on Form 8-K filed on 
     August 6, 1999 and incorporated herein by reference.

(2)  Filed as an exhibit to Registrant's Registration Statement on Form S-8 
     (No. 33-46058) and incorporated herein by reference.

(3)  Filed as an exhibit to Registrant's Annual Report on Form 10-K/A for the 
     fiscal year ended December 31, 1998 and incorporated herein by reference.

(4)  Filed as an exhibit to Registrant's Quarterly Report on Form 10-Q for 
     the quarter ended December 31, 1994 and incorporated herein by reference.

(5)  Filed as an exhibit to NeXstar Pharmaceutical, Inc.'s Quarterly Report 
     on Form 10-Q for the quarter ended June 30, 1997 and incorporated herein 
     by reference.

(6)  Filed as an exhibit to Registrant's Annual Report on Form 10-K for the 
     fiscal year ended December 31, 1998 and incorporated herein by reference.







<PAGE>

August 6, 1999



GILEAD SCIENCES, INC.
333 LAKESIDE DRIVE
FOSTER CITY, CA  94404



Ladies and Gentlemen:

You have requested our opinion with respect to certain matters in connection
with the filing by Gilead Sciences, Inc. (the "Company") of a Registration
Statement on Form S-8 (the "Registration Statement") with the Securities and
Exchange Commission covering the offering of up to Four Million Thirty Thousand
(4,030,000) shares of the Company's Common Stock, $.001 par value, (the
"Shares") pursuant to its 1991 Stock Option Plan, its Employee Stock Purchase
Plan and its 1995 Non-Employee Directors' Stock Option Plan (the "Plans").

In connection with this opinion, we have examined the Registration Statement and
related Prospectus, your Certificate of Incorporation and Bylaws, as amended,
and such other documents, records, certificates, memoranda and other instruments
as we deem necessary as a basis for this opinion. We have assumed the
genuineness and authenticity of all documents submitted to us as originals, the
conformity to originals of all documents submitted to us as copies thereof, and
the due execution and delivery of all documents where due execution and delivery
are a prerequisite to the effectiveness thereof.


On the basis of the foregoing, and in reliance thereon, we are of the opinion
that the Shares, when sold and issued in accordance with the Plans, the
Registration Statement and related Prospectus, will be validly issued, fully
paid, and nonassessable (except as to shares issued pursuant to certain deferred
payment arrangements, which will be fully paid and nonassessable when such
deferred payments are made in full).

We consent to the filing of this opinion as an exhibit to the Registration
Statement.

Very truly yours,

Cooley Godward llp



By:      /s/ Julia L. Davidson
         ---------------------
                  Julia L. Davidson

cc:      Mark L. Perry
         Senior Vice President, Chief Financial Officer and General Counsel
         Gilead Sciences, Inc.



<PAGE>
                                                                   EXHIBIT 23.1


               CONSENT OF ERNST & YOUNG LLP, INDEPENDENT AUDITORS


We consent to the incorporation by reference in this Registration Statement 
(Form S-8) pertaining to the 1991 Stock Option Plan, 1995 Non-Employee 
Directors' Stock Option Plan and Employee Stock Purchase Plan of Gilead 
Sciences, Inc. of our report dated January 21, 1999, with respect to the 
consolidated financial statements of Gilead Sciences, Inc. included in its 
Annual Report (Form 10-K/A) for the year ended December 31, 1998 which is 
incorporated by reference in the Registration Statements (Form S-8 Nos. 
33-46058 and 333-08083) filed with the Securities and Exchange Commission.



                                       /s/ ERNST & YOUNG LLP


Palo Alto, California
August 6, 1999