In mid-2006, Russell was chosen to be a celebrity spokeswoman for CoverGirl cosmetics. In the summer of 2007, Russell appeared in The Keri Kronicles, a reality show sitcom sponsored by CoverGirl and airing on MySpace; the show was filmed at Russell's home in Manhattan and spotlighted her life. Also in 2007, she played Melody on the NBC show Scrubs.
Russell next starred in the film Waitress, which marked the fourth time she played a pregnant woman. Her performance was positively received by critics, with Michael Sragow of The Baltimore Sun writing that Russell's performance had "aesthetic character" and "wields tenderness and fierceness with quiet heat". In 2007, Russell also completed roles in Grimm Love (titled Rohtenburg for its German release), in which she played Katie Armstrong, a graduate student who writes her thesis on an infamous cannibal murder case, and the thriller The Girl in the Park.
Russell next appeared in August Rush, released in November 2007. She also appeared on the cover of the New York Post's Page Six magazine on November 11, 2007. Russell later appeared in Bedtime Stories. In an appearance on The View on December 15, 2008, Russell said she got the part because Adam Sandler's wife Jackie had seen her in Waitress and suggested her for the movie. Russell voiced Wonder Woman in a direct-to-video animated feature released on March 3, 2009.