Conservative Christians played a significant role in pioneering the United States’ groundbreaking anti-HIV funding initiative, the President's Emergency Plan for AIDS Relief (PEPFAR). Consequently, PEPFAR is widely regarded as George W. Bush's crowning achievement. The same political forces that ushered in PEPFAR under President Bush were also the architects of strict ideological restraints around the otherwise straightforward public health goal of curbing the spread of HIV/AIDS. In recent years, some of these restrictions have been rolled back or struck down by the U.S. Supreme Court, and PEPFAR has continued to serve a crucial role in global health and security. PEPFAR's future success in achieving its health mandate (to create an AIDS-free generation) will be influenced by lessons from its past. This article illuminates how, in its first decade, PEPFAR was directed toward the fulfillment of socially conservative goals that ran counter to its official agenda. This was accomplished in large part through two controversial provisions: the “anti-prostitution pledge” (2003–2013) and the “conscience clause” (2003–present). Working in tandem, these policies sought to secure funding for organizations that favored abstinence and fidelity rather than a multisectoral approach to AIDS prevention.