She made her feature film debut in Private School (1983) before having a leading role in Murphy's Law (1986), followed by supporting parts in Witchboard (also 1986), Crossing Delancey (1988), Road House (1989), and Lorenzo's Oil (1992).

[1][6] For her performance in the latter, critic Frank Rich of The New York Times praised her "frisky comic style" and likened her to "Shirley MacLaine in that star's earliest show-biz incarnation.

[1] Next, Wilhoite appeared in the Patrick Swayze-starring Road House (1989), Curtis Hanson's neo-noir Bad Influence (1990), and the drama Lorenzo's Oil (1992).

[1] In film, Wilhoite portrayed the wife of a man who experiences alien abduction in Fire in the Sky (1993), followed by supporting parts in the drama Color of Night (1994) and the survival thriller The Edge (1997), starring Anthony Hopkins and Alec Baldwin.

[8] In 2000, she appeared in several feature films, including the dark comedies Nurse Betty and Drowning Mona, as well as the drama Pay It Forward.

[9] Beginning in late 2003, Wilhoite guest-starred in a recurring role on the series Gilmore Girls, portraying Liz Danes, the mother of Jess Mariano (Milo Ventimiglia).

She subsequently had a supporting part in the comedy King of California (2007), starring Michael Douglas and Evan Rachel Wood.

In 2013, Wilhoite had a supporting part in the romantic comedy Crazy Kind of Love, followed by a central role in the independent drama A Sort of Homecoming (2015).