Fillion has acted in traditionally distributed films like Slither and Trucker, Internet-distributed films like Dr. Horrible's Sing-Along Blog, television soap operas, sitcoms, and theatre. His voice is featured in animation and video games, such as the Bungiegames Halo 3, Halo 3: ODST, Halo: Reach, Destiny, and Destiny 2, along with the 343 Industries game Halo 5: Guardians and the television series M.O.D.O.K. (2021).
Fillion first gained recognition for his work on One Life to Live in the contract role of Joey Buchanan, for which he was nominated for the Daytime Emmy Award for Outstanding Younger Actor in a Drama Series, as well as for his supporting role as Johnny Donnelly in the sitcom Two Guys and a Girl.
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