Specter was Pennsylvania's longest-serving senator when Democrats picked then-U.S. Rep. Joe Sestak over him in the 2010 primary, despite Specter's endorsements by President Barack Obama and other Democratic leaders. Sestak lost Specter's seat to conservative Republican Rep. Pat Toomey by 2 percentage points.
A political moderate, Specter was swept into the Senate in the Reagan landslide of 1980.
He took credit for helping to defeat President Clinton's national health care plan – the complexities of which he highlighted in a gigantic chart that hung on his office wall for years afterward – and helped lead the investigation into Gulf War syndrome. Following the Iran-Contra scandal, he pushed legislation that created the inspectors general of the CIA.
As a senior member of the powerful Appropriations Committee, Specter pushed for increased funding for stem-cell research, breast cancer and Alzheimer's disease, and supported several labor-backed initiatives in a GOP-led Congress. He also doggedly sought federal funds for local projects in his home state.
The former Democrat was not shy about bucking fellow Republicans.
In 1995, he launched a presidential bid, denouncing religious conservatives as the "fringe" that plays too large a role in setting the party's agenda. Specter, who was Jewish, bowed out before the first primary because of lackluster fundraising.