The film received mixed reviews, but she received acclaim for her role and was considered to be a highlight. In 2012, The Forger, in which she played the role of Amber, was released direct to DVD (both this and Hoodwinked Too! Panettiere voiced Kairi in Kingdom Hearts and Kingdom Hearts II, although she was replaced by Alyson Stoner in several sequels; she briefly reprised her role in Kingdom Hearts Birth by Sleep and also voiced Xion in Kingdom Hearts 3D: Dream Drop Distance.
She subsequently starred in 2006's Bring It On: All or Nothing as a cheerleader and had a supporting role as Adelaide Bourbon in the 2007 independent film Shanghai Kiss.
In June 2007, she signed with the William Morris Agency, after previously being represented by the United Talent Agency.
Thanks to her role on Heroes, she became a regular on the science fiction convention circuit, invited to attend conventions around the world in 2007, including Gen Con, New York Comic Con, and Fan Expo Canada.
Panettiere has complained that her acting options are sometimes limited because "people look at [her] as either the popular cheerleader type or just the blonde".
She landed a role as Sarah Roberts on the ABC soap opera One Life to Live from 1994 to 1997, which was followed by Lizzie Spaulding on the CBS soap opera Guiding Light in 1996, and again from 1997 to 2000.
While on Guiding Light, Panettiere's character Lizzie battled leukemia.In early 2007, Panettiere appeared on the MTV show, Punk'd.The appearance was engineered by her mother and involved a male "fan" discussing her work with her, instigating a jealous reaction from the man's spouse.The show reunited Panettiere with Burgess Jenkins (who appears in the first few episodes) from Remember the Titans.The show moved from ABC to CMT for its fifth and sixth seasons, and concluded its run on July 26, 2018.In 2008, Panettiere appeared in the drama Fireflies in the Garden as a younger version of Emily Watson's character, Jane Lawrence.