"[6] In response to the growing AIDS crisis of the 1980s, Edelstein wrote, composed and starred in an original musical called Positive Me which she performed at La MaMa Experimental Theatre Club in New York City, receiving many accolades.

She got her SAG card appearing as a backstage make-up artist in Oliver Stone's Jim Morrison biography The Doors,[9] and then landed a quick series of guest roles on several popular comedies, including Mad About You,[10] Wings,[11] The Larry Sanders Show[12] and Sports Night,[13] where she played a sports reporter who claimed to be a former lover of Josh Charles' character whom he did not remember.

"[15] 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); a transgender woman 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 has often spoken fondly of her experiences on the show and fellow cast and crew, especially her friendship and strong working relationship with Laurie.

[24] Edelstein then joined the award winning The Kominsky Method,[25] a Netflix series that debuted in November 2018, playing the drug addled daughter of Alan Arkin and working alongside such actors such as Michael Douglas, Paul Reiser and Chuck Lorre.

During that time she also reunited with Rob Lowe, playing his ex-wife Gwyneth Morgan, and mother of TK Strand (Ronen Rubenstein) on the ABC drama series, 9-1-1: Lone Star.

She began working with magic marker, and at the suggestion of her artist husband Robert Russell switched to watercolor as the size of each piece grew.