The young actress soon found herself in demand, though. After completing a supporting role in "The Grass Harp", she landed the female lead opposite Vincent Perez in "The Crow: City of Angels" (both 1996). Kirshner then segued to the featured role of Kitty in Bernard Rose's remake of "Leo Tolstoy's 'Anna Karenina'" (1997) and later won the role of a journalist covering a hostage situation in "Mad City" (also 1997). The actress next toiled in several low-profile, non-mainstream films before making the transition to television as a cast member of the werewolf-themed CBS drama "Wolf Lake" (2001). Despite critical praise the series was cancelled early into its first season, but Kirshner returned to the big screen in the youth-film skewering spoof "Not Another Teen Movie" (2001), playing the meanest girl in John Hughes High School. In the little seen but compelling indie "New Best Friend" (2002), Kirshner was especially effective as a nervous, people-pleasing college student who gets drawn into a damaging social circle with disastrous results; and she appeared to great effect in director Bob Clark's spiritual-minded romance "Now & Forever" (2003).

Her profile rose dramatically when she was cast as Jenny Schechter on Showtime's lesbian-centric series "The L-Word" (2004). Her character—a dark, brooding writer fresh from graduating the University of Chicago—recently discovered her sexual orientation and found herself in the center of a circle of Los Angeles lesbians, serving as the lynchpin for the rest of the ensemble that included Jennifer Beals, Pam Grier and Erin Daniels. The polar opposite of Kirshner in real life, her character—impulsive, indulgent and sometimes downright despicable—fluctuated between the gay and straight worlds, falling prey to her erotic desires and moral ambiguity. Utterly fearless, Kirshner relished the challenge of appearing nude in numerous steamy sex scenes, making her a favorite pin-up in the lesbian community. Meanwhile, Kirshner returned to the big screen, costarring in “The Black Dahlia” (2006), Brian De Palma’s take on James Ellroy’s complicated and richly-textured noir thriller about two hard-edged cops (Josh Hartnett and Aaron Eckhart) who descend into obsession, corruption and sexual degeneracy as they investigate the brutal murder of would-be actress Elizabeth Short (Kirshner), who was found tortured and vivisected in a vacant lot in Los Angeles.