Her often frenzied and daring portrayals proved Rajskub an energetic and versatile performer, a reputation she would further prove with stage appearances including the one-woman show "The Littlest Angel,” performed at Santa Monica's Powerhouse Theater in 1996. A guest role on the failed sitcom "The Army Show" (The WB) marked one of the actress' few television appearances until her offbeat comedy met its match in "The Downer Channel" (2001), a Steve Martin-produced sketch series on NBC.
Her film work has included a small role in the 1996 romantic comedy "The Truth About Cats and Dogs" and a part in "Man on the Moon" (1999), Milos Forman's biopic of Andy Kaufman, another concept comedian to whom Rajskub has been likened. A small part in "Magnolia" (1999) and a relationship with score composer Jon Brion allied the actress with Paul Thomas Anderson, who cast her in his as yet untitled follow-up, starring Adam Sandler (and set for a 2002 release). Rajskub would also have memorable scenes in the comedies "Road Trip" and "Dude, Where's My Car" (both 2000) as well as appearing as a guest at "The Anniversary Party" (2001), co-scripted and co-directed by Alan Cumming and Jennifer Jason Leigh. Rajskub got her most prominent film role yet in her friend P.T. Anderson's dark romantic comedy "Punch-Drunk Love," playing one of Adam Sandler's overbearing sisters, who sets him up with his eventual love (Emily Watson).
After a small role in the ‘fiction’ section of Todd Solondz’s bleak comedy “Storytelling” (2002), Rajskub gave an able supporting performance in the Reese Witherspoon-Josh Lucas romantic comedy, “Sweet Home Alabama” (2002). In “Punch-Drunk Love” (2002), she stood out as one of seven sisters constantly haranguing their only brother (Adam Sandler), a socially inept seller of toilet plungers who is set up with her co-worker after getting into trouble with a phone sex operator. Rajskub segued into television with an appearances on “Gilmore Girls” (WB, 2000- ) and “Good Morning Miami” (NBC, 2002-2004), then went back to the feature world, playing a congressional aide brought out of her shell when the effervescent Elle Woods (Reese Witherspoon) heads to Washington, D.C. in “Legally Blonde 2: Red, White and Blonde” (2003).
In 2003, Rajskub began appearing on “24” (Fox, 2001- ) in a recurring role that over three seasons earned the actress a strong fan base and rising celebrity. As Chloe O'Brien, a senior analyst at the Counter Terrorism Unit who serves as a lifeline for agent Jack Bauer (Keifer Sutherland), Rajskub exuded a deft but dour persona despite her off screen charm and exuberance. At first her character had little more to do that spew techno-jargon to Agent Bauer. But as she gained more of a fan club—thanks to her tense delivery of crucial information—the writers developed her character further, even giving her a steamy office romance. Sworn to secrecy by the show’s producers, Rajskub left Chloe’s fate on the show unclear. Meanwhile, she costarred in “Mysterious Skin” (2005), a low budget coming-of-age drama in which she played a Kansas woman whose belief in her abduction by aliens lends a helping hand to unraveling the mystery surrounding a troubled 18-year-old (Brady Corbet) and his possible abduction. Rajskub then had a supporting role in the lame heist thriller, “Firewall” (2006), playing a hipster secretary opposite a miscast Harrison Ford as a computer security specialist forced to embezzle $100 million from a bank after a crew of mercenaries take his family hostage.