Aaron Spelling had cast Cross in the unsold pilot "Temporarily Yours" in 1989 and remembered her when an actress was needed in 1992 to play Dr. Kimberly Shaw on "Melrose Place", Fox's young adult twist on "Beverly Hills, 90210". While simultaneously appearing in "Twelfth Night" in San Diego, Cross began her five season tenure as Kimberly, a doctor whose woes were not related to malpractice. She went from respected doctor to jilted lover to kidnapper to mad bomber to terminal patient. She departed the series and earned Master's Degree in psychology at LA's Antioch University.
In 1999 Cross took a recurring role on the ABC sitcom "Boy Meets World" and enjoyed two guest spots on "King of Queens" in 2002 and 2003, while in between she appeared in episodes of hit series including "Ally McBeal," "Spin City," "Touched By an Angel," "Profiler" and "CSI: Crime Scene Investigation." She also appeared in a string of low-profile films and telepics before returning to series televison on The WB's family drama "Everwood," playing Emily VanCamp's physician mother during 2003-2004 season. But the following year Cross was cast in what would likely be her most memorable role, "Desperate Housewives'" (ABC, 2004- ) very proper, Martha Stewart-esque Wisteria Lane homemaker/control freak Bree Van De Camp, whose picture perfect world hides extremely dysfunctional familial relationships. The mega-popular show breathed new life into Cross' career, and she earned a Golden Globe nomination in 2005 for Best Performance by an Actress in a Television Series - Musical or Comedy. The extra attention also put Cross' personal life in the media glare: in 2005 rumors abounded that the single actress was about to come out as a lesbian with a cover story in The Advocate. As the controversy fanned into a firestorm, the actress did indeed appear in the magazine, but only after proclaiming her heterosexuality to journalists including Babara Walters, noting "I just assume this is what results from being 42 and single."