Her first film appearance was an uncredited cameo in Mrs. Soffel (1984).Her second film appearance was in the television film Student Exchange. In 1986, she appeared on a special "Teen Week" episode of the NBC-TV game show Scrabble. Then she appeared in numerous television commercials, and the sitcom Growing Pains in 1987. In the 1988 teen comedy License to Drive, she co-starred with Corey Haim and Corey Feldman. Her strict parents forbade her to appear in the black comedy, Heathers, which had an expletive-rich script.
Graham has taken roles in mainstream films, including Mary Kelly in the 2001 film From Hell, based on the story of Jack the Ripper, and Judy Robinson in 1998's film Lost In Space, and she has also been cast in a number of independent films. Some of those films, like 2006's Bobby, have brought her critical praise.also starred in the erotic thriller Killing Me Softly.
Graham played herself on one episode of the TV series Sex and the City. In 2003, she appeared in the comedy Anger Management. She was given special guest-star status on nine episodes of NBC-TV's Scrubs during its fourth season (2004–2005), and also appeared as George Michael Bluth's ethics teacher in an episode of Fox's television series, Arrested Development. In 2005, Graham became the spokeswoman and TV model for the Garnier brand of hair care products. Graham's print ad for Skyy vodka, which was photographed in 2003 (titled "#3, Entourage") is still appearing in national magazines today.2003, she also posed for a photoshoot by photographer Sam Jones, during which she was levitated several feet into the air by a magician, who later also sawed her in half.Also in 2003, Graham appeared on the cover of Time magazine for an article titled "The Science of Meditation", indicating that Graham has been practicing Transcendental Meditation since 1991.In 2001, Graham was named by People Magazine as one of the "50 Most Beautiful People". Graham voiced the character of Antonia Bayle in the online role-playing game EverQuest 2.
Graham starred in the US ABC-TV comedy series Emily's Reasons Why Not, in 2006. However, ABC canceled the show after its first airing on January 9, 2006. Graham had posed for a Life Magazine cover story, printed weeks in advance of the assumed series schedule, referring to her as "TV's sexiest star" which appeared two weeks later in their January 27, 2006 issue.In 2009, she played the stripper Jade in The Hangover. The film was released to critical and box office success.[ next film will be the family comedy Judy Moody and the Not Bummer Summer.