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.
Despite his tireless campaigning, Specter's irascible independence caught up with him in 2004. Specter barely survived a GOP primary challenge by Toomey by 17,000 votes of more than 1.4 million cast. He went on to easily win the general election with the help of organized labor, a traditionally Democratic constituency.
Specter startled fellow senators in April 2009 when he announced he was switching to the Democratic side, saying he found himself "increasingly at odds with the Republican philosophy." Earlier in the year, he had been one of only three Republicans in Congress — and the only one facing re-election in 2010 — who voted for President Barack Obama's economic stimulus bill.
He also said he had concluded that his chance of defeating a GOP challenger in the 2010 party primary was bleak. But he said the Democrats couldn't count on him to be "an automatic 60th vote" to give the party a filibuster-proof majority.