Smart would reach her widest audience with a co-starring role opposite James Van Der Beek in Brian Robbins' surprise box office hit "Varsity Blues". The actress played Jules Harbor, a girl who longs for life beyond her small town's high school football-obsessed culture but who, as sister of the injured star quarterback (Paul Walker) and girlfriend of his idealistic replacement (Van Der Beek), is tied to it. With her darkened hair, sad eyes and intelligent portrayal of the strong-willed Jules, Smart reminded audiences of Van Der Beek's "Dawson's Creek" co-star Katie Holmes. She would next be featured as Shawn Hatosy's upper-class love interest in Michael Corrente's poignant 1970s era comedy "Outside Providence". Based on Peter Farrelly's novel, the film followed a working-class teenaged boy (Hatosy) sent by his abrasive but loving father (Alec Baldwin) to a tony prep school after running into trouble at home. Later that year, Smart joined the cast of The WB's "Felicity" with a recurring turn as the new arrival who takes up with resident advisor Noel after the indecisive title character breaks his heart.

Again playing off her somewhat retro looks, she next assumed one of the leading roles in the NBC miniseries "The 70s" (2000) as one of four friends who graduate at the dawn of the 'Me Decade.' She received more mainstream exposure--literally, given a provocative topless scene--among youth audiences with her risqué but sweet turn in the vulgar Tom Green campus comedy "Road Trip" (2000), as the college girl who seduces Breckin Meyer, only to have their tryst end up on a videotape inadvertently mailed to Meyer's girlfriend. She played a 70s hippie chick again in "Scotland, Pa." (2001), writer-director Billy Morrissette's loopy version of "Macbeth" set amid fast food outlets and shag carpets, and she was one of the wacky ensemble in "Rat Race" (2001), paired again with Meyer as a beautiful helicopter pilot helping him seek out a $2 million prize, only to prove to be imbalanced when she launches a bizarre, jealous air assault on her boyfriend when she sees him frolicking in a pool with an ex.

A large TV audience became familiar with her during a multi-episode stint on the NBC sit-com "Scrubs" when Smart played Jamie, the grieving young wife of a comatose man who becomes attracted to J.D. (Zack Braff). The two begin a guilty relationship, and upon the husband's death she begins to demand similar drama in their day-to-day lives. Smart became a regular part of the second season of HBO's let's-make-a-movie series "Project Greenlight" in 2003 after she was cast in tyro filmmakers' movie "The Battle of Shaker Heights" (2003) as the faraway object of a young man's affection. Smart was depicted as game and agreeable behind the scenes, though often flummoxed by the filmmakers' passive-aggressive and often hard-to-fathom directing style.

She was paired with Ashton Kutcher in the uneven sci-fi melodrama "The Butterfly Effect" (2003), playing Kutcher's leading lady, who lives through various revised lives as his attempts to fix their troubled pasts alters the timeline. After a small part as a nurse in the romantic comedy “Win A Date With Tad Hamilton!” (2004), Smart provided mild titillation as a cheerleader in the action-comedy “Starsky & Hutch” (2004). In the conspiracy thriller “Blind Horizon” (2004), she played a nurse drawn to a wounded man (Val Kilmer) found in the desert who claims to have knowledge of an assassination plot against the President of the United States. A small role in the barely seen sex comedy “National Lampoon’s Barely Legal” (2005) was soon followed by a leading performance in the mainstream comedy, “Just Friends” (2005), wherein she played the high school best friend of a shy and overweigh teen (Ryan Reynolds) whose crush on her never went away even after growing up to become a suave and successful music executive.