After a cameo in "EDtv" (1999) and a recurring role on ABC's "Once and Again" (2000), Holden hit the big time with a recurring role on "Friends". As Elizabeth, the co-ed professor Ross (David Schwimmer) inappropriately dates, the actress did a nice job balancing her character's very adult feminine wiles and her juvenile quirks. Beautiful and forthcoming, she was alluring enough that Ross would risk his job, but at the same time she irritated him with her unwillingness to commit, tendency to perform childish pranks and her running-wild, spring break behavior caught on tape. When Bruce Willis guested as Elizabeth's father on the series, Holden got her first taste of superstardom, but it's a safe bet that it won't be her last.
2001 saw the actress join the ensemble of the dark teen comedy "Sugar & Spice" playing Fern, the new cheerleader recruit who is allowed on the squad despite her apparent lack of skill and soap as a trade for arms. When a group of cheerleaders (Marley Shelton, Mena Suvari, Rachel Blanchard, Melissa George, Sara Marsh) decides to rob a bank in order to support an expected baby, their quest for guns leads them to Fern, whose father lowers the bill in return for his daughter having a spot on the squad. Stringy hair, bad posture and a dirty face almost made Holden unrecognizable, and unlike most movies of the genre, her transformation was neither quick nor completely successful, but her character was able to contribute significantly to the heist. Next up for the actress was a recurring role on Fox's "Ally McBeal" in 2001.
Lensed in 2000, the horror thriller "Wishcraft" promised to win the actress a genre following, while the 2001-lensed mystery "American Gun" would cast her as the granddaughter of James Coburn's sharp-witted World War II vet out to solve the murder of his daughter. In 2002, along with appearing in small, adventurous indies like the thriller "Purgatory Flats" and the comedy "Moving Alan" Holden was seen by large mainstream audiences opposite Rob Schnieder in the gender-bending comedy "The Hot Chick" as Lulu, one of the gal pals of the body-swapped sorority girl, and she also made an impression as a Hollywood party girl who suffers a girsly fate in an opening sequence of the acclaimed HBO series "Six Feet Under." The actress was next cast as Mandy Moore's man-hungry best friend Scarlett in the teen romance "How to Deal" (2003).