Villar ran for Senator in the 2001 election. Having recently resigned from Estrada’s LAMMP coalition, he ran for Senator as an independent politician, but campaigned as a member of the People Power Coalition, the administration coalition party which was supportive of the recent 2001 EDSA Revolution. He was elected to the Senate with more than 11 million votes, ranking seventh out of 37 candidates. He later won re-election in 2007, running as a member of the Genuine Opposition coalition, ranking fourth out of 37 candidates.
In July 2006, Villar was chosen Senate President, making him the first post-World War II public official to head both the House of Representatives and the Senate. He had previously held the position of Senate President pro tempore, as well as the chairmanship of the Committees on Finance, Foreign Relations, Public Order, and Committee on Agriculture and Fisheries.