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She also starred as the lead role of Abby McCarthy in the Bravo series Girlfriends' Guide to Divorce, an hour-long comedy-drama loosely based on the book series by Vicki Iovine and which premiered on December 2, 2014. In 2018, Edelstein joined the cast of ABC's The Good Doctor in season two as Dr. Blaize in a recurring role. This reunited her with House creator David Shore. Edelstein also plays a recurring character in The Kominsky Method, a Netflix series that debuted in November 2018.

On May 25, 2014, Edelstein married artist Robert Russell in Los Angeles.

In May 2011, Edelstein announced that she would not return for the eighth and final season of House. Starting in June 2011, she began an arc on The Good Wife as lawyer Celeste Serrano. She guest-starred in Scandal in 2013, and later three episodes of the ABC series Castle.

Edelstein is a supporter of Best Friends Animal Society, of which she is an Ambassador. She supports human rights organizations and is a patron of the arts. She has appeared in numerous magazines, including the September 2010 cover of H magazine. She posed for PETA in an ad promoting vegetarianism, a diet she has followed for most of her life.

From 2004 to 2011, she portrayed her biggest and most notable role to date, Dr. Lisa Cuddy, the Dean of Medicine at Princeton-Plainsboro Teaching Hospital and frequent adversary, friend, and eventual girlfriend of title character Gregory House (Hugh Laurie) on Fox's TV series House. Edelstein has often spoken fondly of her experiences on the show and fellow cast and crew, especially her friendship and strong working relationship with Laurie.

She moved to New York City at the age of 18 to study theatre at New York University's Tisch School of the Arts. While living in New York, she became involved in the club scene (known there only as "Lisa E") and caused enough of a stir in the community to be dubbed New York City's "Queen of the Night" by writer and fellow celebutant James St. James, who briefly refers to Edelstein in his 1999 book Disco Bloodbath.

Bigger roles in TV dramas soon followed, among them the lesbian sister on ABC's Relativity (1996); a high-priced call girl turned Rob Lowe's date on The West Wing (1999); an assigned male at birth (AMAB) transwoman on Ally McBeal (2000); and Ben Covington's (Scott Speedman) girlfriend on Felicity (2001). She also continued to land guest-star spots on such shows as ER, Frasier, Just Shoot Me!, Without a Trace, and Judging Amy, as well as small parts in the films What Women Want, Keeping the Faith, As Good as It Gets, and Daddy Day Care.

Edelstein was born in Boston, Massachusetts, to Bonnie and Alvin Edelstein. Her father is a pediatrician at Chilton Memorial Hospital (since retired). The youngest of three children in a Jewish family, she was raised in Wayne, New Jersey, and attended Wayne Valley High School, graduating in 1984.

After being dubbed a "celebutante" by The New York Times magazine during her club kid days, Edelstein used her new-found celebrity to write, compose and star in an original musical called Positive Me in response to the growing AIDS crisis of the 1980s. The play, performed at La MaMa Experimental Theatre Club in New York City, received many accolades. After an unsuccessful stint hosting Awake on the Wild Side for MTV in 1990, she appeared as a backstage make-up artist in Oliver Stone's Jim Morrison biography The Doors, followed by guest roles on several popular comedies, including Mad About You, Wings, and The Larry Sanders Show. On Sports Night, she played a sports reporter who claimed to be a former lover of Josh Charles' character whom he did not remember. On Seinfeld, she played George Costanza's sexually frustrated girlfriend in the episode "The Masseuse",

Lisa Edelstein (/ˈ l iː s ə ˈ ɛ d əl s t iː n / ; born May 21, 1966) is an American actress and playwright. Edelstein is known for playing Dr. Lisa Cuddy on the Fox medical drama series House. Between 2014 and 2018, she starred as Abby McCarthy in the Bravo series Girlfriends' Guide to Divorce.