Twenty years ago, under the administration of George W. Bush, the US government established the President’s Emergency Plan for AIDS Relief (PEPFAR). With allocations exceeding $110 billion, it represents the largest investment ever made by any nation in a single disease. The resulting package of testing, prevention, and treatment is credited with saving more than 25 million lives. Learn how PEPFAR happened, and why continued commitment is vital, from two men who made the initiative possible—long-time NIAID head Tony Fauci, who conceptualized the strategy, and Bill Frist, former US Senate majority leader (R-TN), who helped move authorizing legislation through Congress.