Fiorentino got her first professional role in 1985 when she starred in Vision Quest. It was not until 1994 that she became widely recognized, receiving accolades for her performance in The Last Seduction as femme fatale Bridget, almost the textbook example of a murderous seductress in a modern film noir. Because it was first aired on HBO television she was ineligible for an Academy Award nomination for Best Actress, despite glowing reviews.

She later worked again with director John Dahl, who cast her in his film Unforgettable. Her co-star from Gotcha!, Anthony Edwards, has also directed her in one of his films.

The 1995 erotic thriller Jade, directed by William Friedkin, was expected to enhance the actress's status as a sex symbol, but the movie turned out to be a critical and commercial failure. Fiorentino was placed 66th on a list of "100 Sexiest Stars in Film History" by Empire magazine.

Fiorentino has developed a reputation as a difficult actress to work with.