Her father, Tom Tripplehorn, was a guitarist with Gary Lewis & The Playboys.
Graduated in 1981 from Edison High School in Tulsa. Spent one semester at the Tulsa University.
Studied in the Drama Division of The Juilliard School at Lincoln Center in New York City. Was a member of Group 19 (1986-90), which also included Laura Linney.
On 5/23/02 son August Tripplehorn Orser, born at Cedars-Sinai Medical Center (Los Angeles), 7 lb. 8 oz.
Replaced Robin Wright, due to pregnancy, as Abby McDeere in The Firm (1993) with Tom Cruise.
She was originally cast as "Mia Wallace" in Quentin Tarantino's Pulp Fiction (1994), but had to turn down the role. She was replaced by Uma Thurman.
Has a younger brother who is a drummer/rock musician. He appeared briefly in Reality Bites (1994) as the drummer of Ethan Hawke's band, but was not credited.
Was the original choice for the female lead in Four Weddings and a Funeral (1994). Prior to leaving for the UK to begin filming, stopped off in Texas to see her mother. As her mother was walking towards Jeanne to greet her, she collapsed and died instantly. As a result, Andie MacDowell stepped in and played the role.
Was considered for the role of Dr. Chase Meridian in Batman Forever (1995).
Spokesperson for the World Monuments Fund. 
Nominated as Outstanding Actress in a Made For Television Movie in The Women's Image Network (WIN) Awards 2012 for her work the film FIVE.
Criminal Minds: The Pact (2012) is her first appearance, as part of the team, as Agent Alex Blake.