Specter outspent Sestak, a retired Navy vice admiral, but Sestak attacked him as a political opportunist who switched parties to save his job. A memorable campaign ad used Specter's own words against him: "My change in party will enable me to be re-elected."
Specter was diagnosed in February 2005 with stage IV Hodgkin's disease, a cancer of the lymphatic system. Announcing the diagnosis with his trademark doggedness, Specter said: "I have beaten a brain tumor, bypass heart surgery and many tough political opponents and I'm going to beat this, too."
He wrote of his struggle in a 2008 book, "Never Give In: Battling Cancer in the Senate," saying he wanted to let others facing similar crises "ought to know they are not alone."
Cancer handed him "a stark look at mortality" and an "added sense of humility," Specter told The Associated Press.
Intellectual and stubborn, Specter played squash nearly every day into his mid-70s and liked to unwind with a martini or two at night. He took the lead on a wide spectrum of issues and was no stranger to controversy.
Born in Wichita, Kan., on Feb. 12, 1930, Specter spent summers toiling in his father's junkyard in Russell, Kan., where he knew another future senator — Bob Dole. The junkyard thrived during World War II, allowing Specter's father to send his four children to college.
Specter left Kansas for college in 1947 because the University of Kansas, where his best friends were headed, did not have Jewish fraternities. He graduated from the University of Pennsylvania in 1951 and Yale law school in 1956. He served in the Air Force from 1951 to 1953.
Friends say his childhood circumstances made him determined, tough and independent-minded. Specter considered his father's triumphs the embodiment of the American dream, a fulfillment that friends say drove him to a career in public life.