In the early 2000s, Russell mainly appeared in low-budget and independent films, such as The House Next Door (2002), Now & Forever (2002), and The Box (2003). In 2005, she was cast in the role of Charlene in the HBO mini-series Empire Falls, opposite Ed Harris. She also appeared in the supporting role of Emma Marko in Spider-Man 3 as the wife of Flint Marko (Thomas Haden Church). Spider-Man 3 was a major box office success, grossing nearly $900 million worldwide. The following year, she appeared in the independent drama Jolene, starring Jessica Chastain, and also had a minor role playing the mother of Scarlett Johansson's character in the romantic comedy He's Just Not That into You (2009), though her scenes were eventually cut from the film.