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In addition to performing as the voice of Lisa Simpson on The Simpsons, Smith also appeared on the sitcoms Herman's Head and Dharma and Greg and guest-starred on Showtime's Dead Like Me and the Disney Channel's Phil of the Future. Her résumé features guest appearances on Teen Angel, and the "Mathnet" segment of the Children's Television Workshop show Square One. She also appeared as an escaped juvenile prisoner named "Bonita Rokeke" in an episode of Mama's Family.

Her film credits include The Legend of Billie Jean, City Slickers, Maximum Overdrive and As Good as It Gets. A twist of trivia regarding her work on The Simpsons was that she auditioned for the role of Bart Simpson, while Nancy Cartwright auditioned for the part of Lisa. However the producers felt that Smith would be better suited for Lisa's voice, while Cartwright was given the role of Bart.

Smith won an Emmy for Outstanding Voice-Over Performance for her work on The Simpsons in 1992. Lisa's distinctive voice differs from Smith's only in that it is higher in pitch. Smith has joked about her lack of vocal range in comparison to her Simpsons co-stars, saying she only has three voices: her own, Lisa's, and one that's somewhere in between. She has also said that any time Lisa sings on the show that she has to drop into her own singing voice. Her laugh however, as heard on the season 8 DVD commentaries is quite close to Lisa's. (wikipedia.org)