By this time, her sharp, dark beauty had brought her to the attention of Hollywood. Neuwirth began doing cameos as Frasier Crane's repressed siren wife on "Cheers" (NBC). She continued as a semi-regular character through 1992, and has reprised the role from time to time on the spin-off "Frasier" (NBC, 1993-2004). Her other TV work has been spotty. Neuwirth had supporting roles in the 1990 dramas "Without Her Consent" (NBC), as famed attorney Gloria Allred, and "Unspeakable Acts" (ABC). She also appeared on the short-lived dark fantasy series "Wild Palms" (ABC, 1993). "Dear Diary", a failed ABC sitcom pilot in which Neuwirth portrayed an editor and diarist, was released in 1996 as a short film and won an Oscar as Best Short Subject.
Neuwirth has appeared in a handful of films, few of which have exploited her peculiar, dry talents. She debuted as a guidance counselor in "Say Anything" (1989) and had supporting roles in "Green Card" (1990), as Andie MacDowell's best friend, and in "Bugsy" (1991), as the real-life socialite Countess di Frasso. In the effective thriller "Malice" (1993), Neuwirth was the detective trailing Alec Baldwin while in "Jumanji" (1995), she was the aunt of the children who begin playing a mysterious board game. She had perhaps her best role to date in a distinct change of pace as a sexy yuppie in "The Associate" (1996). Additionally, she has also loaned her talents to the kiddie films "All Dogs Go to Heaven 2" (as a voice-over) and "The Adventures of Pinocchio" (both 1996).
But it is onstage that Neuwirth has always been happiest and most effectively utilized. Her combined skills as actor, dancer and singer have been seen in the musical revue "Showing Off" (New York, 1989), as Lola in the 1994 revival of "Damn Yankees" and in the 1996 revival of "Chicago" on Broadway. In the latter, her portrayal of celebrity murderess Velma Kelly (originated by Chita Rivera in 1975) earned her rave reviews and she all but overshadowed co-stars Ann Reinking, James Naughton and Joel Gray. Neuwirth picked up a second Tony Award for her efforts.
Neuwirth had memorable roles in several feature films over the next five years, including playing a hooker in Woody Allen's film "Celebrity" (1998). Neuwirth had leading roles in two well-received television movies as well, 1999's "Dash and Lilly" and 2000's "Cupid & Cate."
In 2002, Neuwirth played a sexy chiropractor who seduces a 15 year old boy who is in love with his stepmother (Sigourney Weaver) in "Tadpole." The movie was a hit with critics and a perfect showcase for Neuwirth's subtle, out-of-the-ordinary style. She took a supporting role in the romantic comedy "How to Lose a Guy in 10 Days" (2003) playing a no-nonsense New York fashion editor opposite Kate Hudson, with whom she was also featured in "Le Divorce" (2003), and the actress was featured in the Elmore Leonard-penned caper comedy "The Big Bounce" (2004).
The actress continued to foray back to the small screen, with a recurring role on the short-lived cabbie drama "Hack" (CBS, 2003), an especially amusing stint playing herself on a 2004 episode of "Will & Grace," and her eventual return to regular series work playing assistant district attorney Tracey Kibre in yet another spin-off of NBC's legal crime drama franchise, "Law & Order: Trail By Jury" (2005 - ).