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Shiri Freda Appleby e seu irmão Evan se criaram em São Fernando, a noroeste de Los Angeles, seu pai Jerry é executivo e sua mãe, Dina, é professora. Quando criança levou uma mordida de cachorro acima do olho, o que lhe deu uma cicatriz que dura até hoje, por causa da mordida, desenvolveu um medo de cães de teve de ser tratada com psiquiatras, após o tratamento, adotou a cadelinha Tabby. Shiri estudou na universidade de Calabassas em 1997, onde se formou em literatura.
Shiri começou a sua carreira aos 4 anos anunciando produtos como M&M. Teve aparições diversas na TV em 1980-2000, em séries como Thirtysomething (1987), Doogie Howser, M.D (1989), Xena: Warrior Princess (1998). Para a série Roswell tentou 2 papés (Isabell e Maria) antes de ser chamada para representar Liz Parker. Shiri esteve presente no músical "Its my life" de Bon Jovi's. Apareceu num outro musical, "I Don't Want To Be", de Gavin DeGraw. Até 2006 Shiri podia ser vista no Drama Six Degrees como a jovem Anya. Desde 2007 namora o ator Zach Braff.
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