He is known for his starring roles as Hardy Jenns in Some Kind of Wonderful (1987), Aaron "Cabal" Boone in Nightbreed (1990), Norman Maclean in A River Runs Through It (1992), Joe Kane in The Program (1993), Joseph in Bliss (1997), and as Keith Scott on the television series One Tree Hill (2003–12).
He attended East Stroudsburg University of Pennsylvania for two years on a sports scholarship, playing baseball and football, until sustaining a knee injury.
[4] After appearing in commercials, Sheffer was first seen on a nationwide basis as Ian Hayden on the ABC daytime soap opera One Life to Live in 1982, and on the short-lived primetime drama The Hamptons in 1983.
In 1984, he was cast in his first film role, as the romantic lead opposite Pia Zadora in the genre-bending musical Voyage of the Rock Aliens.
In 1992, Sheffer starred as author Norman Maclean in the Oscar-winning biographical film A River Runs Through It, directed by Robert Redford.
He directed the feature film American Crude, a dark comedy starring Ron Livingston and Rob Schneider; it was released straight to DVD in June 2008.