This chapter explores the development of President's Emergency Plan for AIDS Relief (PEPFAR), its principles, processes and practicalities, as part of a wider analysis of the President George W. Bush administration's contribution to tackling the challenge of HIV-AIDS internationally. It considers what the implications of such financial and technical assistance were for the 'soft power' of the administration with a number of related audiences. Using the Clinton administration's own figures, in 1998 HIV-AIDS globally caused 2.3m deaths, a 'dramatically' significant increase from the 0.7m registered in 1993, with a declassified National Intelligence Estimate (NIE) forecasting that 'HIV-AIDS will probably cause more deaths than any other single infectious disease worldwide by 2020'. Having analysed the contribution of the Bush administration to combatting the spread of HIV-AIDS in both its bilateral and multilateral guises, it is worth also highlighting the functional impact of such efforts, which have drawn much praise internationally.