As the AIDS pandemic escalated, it was essential that the global community had a leader to coordinate and direct its response, and the Global Programme on AIDS (GPA) was pivotal in this role. As its new Director, Michael Merson made essential organizational changes within GPA to improve the Program’s performance and increase donor confidence in GPA’s leadership. This chapter describes how GPA strengthened the global response by: containing the global spread of HIV; reviewing and enhancing the performance of national programs; addressing human rights; and improving coordination. We detail how Merson navigated the internal politics of the World Health Organization (WHO), as he undertook to shift more responsibility from GPA in WHO headquarters to the WHO regional offices. This chapter also covers GPA’s efforts to continue a close partnership with non-governmental organizations and advocacy groups.