The United States President's Emergency Plan for AIDS Relief (PEPFAR), launched by President Bush with strong bipartisan support, was a historic moment in development both in size and scope. With $18.8 billion across its first 5 years, it is the largest international health initiative in history for a specific disease. In scope, it is the first global initiative to tackle a chronic disease and was based in a new philosophical foundation centered in country ownership, a results-based accountable approach, the engagement of all sectors, and good governance. With resources and a strong intellectual base, PEPFAR saved lives and provided lessons learned for effective development.