Gershon moved to New York City from Boston to attend NYU, where she studied drama and child psychology. She also attended Circle in the Square Professional Theater School in New York, working with David Mamet and Harold Guskin. She is one of the founding members of the New York based theater group, Naked Angels.

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 but