At Sony Pictures Entertainment, Ziskin served as a producer on all three Spider-Man films directed by Sam Raimi, and that trilogy became the biggest franchise in Sony's history. She was a major creative force behind all three entries, and despite her illness, she had been hard at work on next summer's reboot The Amazing Spider-Man.
Ziskin was a graduate of the USC School of Cinematic Arts and she earned her first associate producer credit on Eyes of Laura Mars in 1978, after having worked for producer Jon Peters. Following that, she joined Sally Field in creating Fogwood Films, through which she produced Murphy's Romance and No Way Out.
In 1990 she was a pivotal part of making Pretty Woman a huge box office success that has spent the subsequent twenty years in the zeitgeist. As an executive producer on the Garry Marshall-directed film, she made creative contributions that helped create a feel-good romantic comedy as opposed to a downbeat story of a prostitute who has a doomed relationship with a wealthy man.
With her husband Sargent, who also took the final pass at each and every Spider-Man script, Ziskin created the stories for both What About Bob? and Hero. In 1997, she produced the critically lauded, Oscar-winning drama As Good as It Gets, which was written and directed by James L. Brooks. For the second half of the 1990s, she served as President of Fox 2000, which released memorable films such as Fight Club, Courage Under Fire, The Thin Red Line, Soul Food, and Never Been Kissed.
In 2002, Ziskin became the first woman to produce the Oscar telecast, and she returned to her role as executive producer in 2007. Earlier this year, she received the Producers Guild of America's Visionary Award, after having been honored with the Guild's David O. Selznick Lifetime Achievement Award in 2005. She was a rare woman to ascend to the highest levels in the traditionally male-dominated movie industry.
She was diagnosed with cancer in 2004, while working on Spider-Man 2. She subsequently co-founded Stand Up 2 Cancer, and executive produced two televised specials which raised millions of dollars to be donated to various aspects of cancer research and the fight against the disease. Her family requests that donations in her memory be made at Stand Up 2 Cancer.