Raised in Fort Worth, Texas, Harris began in the theater after graduating from Juilliard, spending three years as a member of The Acting Company. She also appeared in regional theater productions at the Long Wharf and Yale Rep. In 1986, Harris was Ophelia to Kevin Kline's "Hamlet" (with future "Frasier" co-star David Hyde Pierce as her brother Laertes). Paul Rudnick wrote the female roles in his 1993 Off-Broadway hit "Jeffrey" especially for the actress. (She also appeared in the L.A. premiere).

By the late 1980s, Harris had broken into TV, appearing in episodic guest shots on such series as "Doctor, Doctor" and "Law & Order". In 1993, Harris made her TV-movie debut in "Dead Drunk: The Kevin Turrell Story" for HBO. Her feature appearances, however, have been limited. Harris briefly appeared as one of the mothers whose children were attending camp in "Addams Family Values" (1993), scripted by Rudnick, and was secretary to producer Dan Enright (David Paymer) in Robert Redford's Oscar-nominated "Quiz Show" (1994).

Harris' profile escalated dramatically when she took on the role of the conniving Bebe during "Frasier's" first season in 1993, making regular appearances throughout the series' 11-year run. She then started snaring regular roles, playing the obnoxious class-conscious daughter-in-law Vivian Buchanan on clever but low-rated sitcom "The Five Mrs. Buchanans" (CBS, 1994-95), returned to the weekly series format as Suzanne, an embittered real estate agent, on the NBC sitcom "Union Square" (1997-98), had a recurring roll on the short-lived sitcom "Stark Raving Mad" (NBC, 1999-2000) and appeared in the brief ABC journalism drama "The Beast" (2001) as Mrs. Sweeny, the primary manager of the life of the head of a 24-hour TV news network, whose edgy wit and brutal honesty keeps the staff in tow. She next appeared as a regular on "It's All Relative" (ABC, 2003) as the blue-collar mother who's son is in love with a woman raised by two gay men. In between gigs, Harris racked up dozens of guest-starring credits o n a slew of televison comedies and dramas, including "The X-Files," "Murphy Brown," "Sisters," "Chicago Hope," "The Practice," "Ally McBeal," "Six Feet Under" and "CSI: Crime Scene Investigation." At the end of 2004 she began a string of appearances on the smash hit "Desperate Housewives" as a character who may hold answers to the mysteries that drove the series.

Televison wasn't the only medium to embrace Harris. She appeared in a diverse array of feature films, including Baz Luhrrman's eye-popping modernization of Shakespeare, "Romeo + Juliet" (1996), the appealing dark comedy "Nurse Betty" (2000), Christopher Nolan's inventively told thriller "Memento" (2000), the Jet Li action-fest "The One" (2001) and the Jennifer Lopez-Jane Fonda comedy "Monster-In-Law" (2005).

Her busy Hollywood schedule was balanced with a steady roster of stage work. She appeared in the Roundabout Theater Company's 2000 New York revival of the classic Kaufman-Hart comedy "The Man Who Came to Dinner" about a famous (and famously acid-tongued) theater critic who is forced to stay in a Midwestern couple's home. Harris appeared opposite Nathan Lane and Jean Smart as Maggie Cutler, Lane's devoted secretary and Smart's nemesis, and one of the performances was broadcast live on PBS's "Stage on Screen" program. Harris took home 2001-02 Tony Award for Best Performance by a Featured Actress in a Musical for her work as Mrs. Meers in the stage version of "Thoroughly Modern Millie," and she made her debut with the New York Philaharmonic in April 2003 in the role of Beatrice,in the concert staging of Berlioz's opera "Beatrice and Benedict" opposite her "Frasier" co-star David Hyde Pierce.