She was born in Chicago, IL and after university she moved to to stages on broadway. Henner came to national prominence with the role of Elaine Nardo in the television series Taxi. She was the leading lady in the 1984 film Johnny Dangerously, playing love interest to Michael Keaton. She also appeared in Noises Off (1992), and in Man on the Moon (1999), a film about her Taxi co-star Andy Kaufman, she played both herself and her Taxi character.
She has authored seven books on diet and health, the most prominent being Total Health Makeover, in which she explains the virtues of a non-dairy diet in conjunction with food combining & exercise.
Henner was a contestant on the NBC show The Celebrity Apprentice. She was fired by Donald Trump in the 8th episode, but was brought back to help fellow contestant Trace Adkins in the final task of the show.