In 2000, Gregson Wagner had roles in "Stranger Than Fiction", and "High Fidelity" opposite John Cusack. In 2001, she was regular cast member in the short-lived prime time soap opera, "Pasadena". In 2003, she played Barbara Richardson in the movie "Wonderland". In 2004, she had a role in the Hallmark movie, "Angel in the Family" playing the part of Beth. In 2005 Gregson Wagner guest-starred on "Cold Case" and "Medium". In 2006, she starred in two episodes of "ER": "Bloodline" and "21 Guns". From 2005 to 2007, she had a recurring role on the TV show "The 4400" as April Skouris, the sister of NTAC agent Diana Skouris. In 2008, she guest starred on "" and "House M.D".