Lisa Edelstein began her professional acting career while studying theater at N.Y.U.'s Tisch School of the Arts. After performing in a wide range of productions off and on Broadway, authored and performed the AIDS-related musical "Positive Me" at Ellen Stuart's La Mama, in Manhattan. It was one one of the earliest AIDS-related theater productions.

Lisa gained her first television experience as a host of the cable series Awake on the Wild Side (1990). In the last several years, she has fearlessly taken on a wide variety of roles for television. She played a call-girl girlfriend on The West Wing (1999), David Conrad's sister on Relativity (1996), the transgender girlfriend of James Le Gros on Ally McBeal (1997) and an Orthodox Jewish woman on Family Law (1999). She also played James Spader's love interest on The Practice (1997), and has had numerous other TV roles and guest appearances.

From 2004-2011, she played the hospital administrator Dr. Lisa Cuddy on the hit medical drama House (2004).