A 2008 Vanity Fair article linked her romantically with former President Bill Clinton. Speaking on the U.S. television show Live with Regis and Kelly on June 9, she said, "It is such a crazy, outrageous lie.... I met him three times at events. It disturbed me on so many levels. I felt I had to stand up and say the truth.
Her first acting venues were stage appearances in Camille and The Substance of Fire. Her break came with a bit part in 1986's Pretty in Pink, and then a bigger part in Cocktail with Tom Cruise. Gershon also worked in TV, with a recurring role on Melrose Place. She won critical acclaim for her portrayal of Nancy Sinatra in the made-for-TV bio-pic, Sinatra. In 1996, she played Corky, an ex-con who gets mixed up in a lesbian affair with Jennifer Tilly, in the mobster flick, Bound. The following year she co-starred with John Travolta and Nicolas Cage in Face/Off.
Gershon is regarded as a gay icon because of her roles in movies such as Bound (in which she played a butch lesbian), "Prey For Rock & Roll"" and Showgirls (which is regarded as a camp classic). At the same time, her sultry good looks and frequent nude appearances in other films have also gained her a substantial heterosexual male fan base. She was ranked #51 on the Maxim Hot 100 Women of 2004.
Gershon played Jew's harp on "I Can't Decide", a song on the Scissor Sisters 2006 release Ta-Dah. She also played Jew's harp on the song "I Do It For Your Love", Paul Simon's collaboration with Herbie Hancock on his album Possibilities. On television, she has recurring roles on HBO's Curb Your Enthusiasm (as a Hasidic drycleaner), Rescue Me, and the U.S. dramedy series Ugly Betty (as Italian cosmetics mogul Fabia, the rival of Wilhelmina Slater). She also has served as the voiceover for Major League Baseball's "I Live For This" promotional campaign.
She and her brother Dann are the authors of the children's book Camp Creepy Time.