- Was born in Paris, but raised in Washington, DC; her father, Joseph Yeardley Smith, was the first official editor for the Washington Post's obituary desk.
- Got her big break in 1984 when, as an understudy, she took over Cynthia Nixon's role on Broadway in The Real Thing.
- Made her TV debut in the 1984 ABC Afterschool Specials production Mom's on Strike.
- The Simpsons producer Bonnie Pietila wanted Smith for the series after seeing her play a knife-wielding tomboy in the play Livin' on Salvation Street in Los Angeles .
- Originally read for the role of Bart Simpson, with co-star Nancy Cartwright reading the part of Lisa, who eventually became Smith's character.
- In 2004, performed a one-woman show titled More, in which she candidly discussed her lonely childhood, plastic surgeries and decades of battling bulimia.
- Published a children's book titled I, Loreli, in 2009.
- Launched her own shoe line, Marchez Vous, in 2011.
- 1992, Emmy — Outstanding Voice-Over Performance: Winner
- Joseph Yeardley Smith — Father
- Christopher Grove — Ex-husband
- Martha — Mother
- Marian Ambrose Smith — Stepmother
- Hope Smith — Stepsister
- Thomas Smith — Brother
- Daniel Erickson — Ex-husband
- Henry Smith — Stepbrother
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