Chapter 5 presents the book’s second comparative case study, which examines four major global health agencies: the World Health Organization (WHO); the Joint United Nations Programme on HIV/AIDS (UNAIDS); Gavi, the Vaccine Alliance; and the Global Fund to Fight Aids, Tuberculosis and Malaria (GFATM). The structure of the examination is analogous to Chapter 4’s. After enumerating the characteristics on which the four institutions are matched, I chronicle how differences in their de facto policy autonomy have given rise to disparate performance outcomes: The WHO and UNAIDS have been characterized by relentlessly declining autonomy and performance over their life cycles, Gavi and GFATM by the opposite trends. I then delve into the operational origins of these differences, which, once again, defy a purely design-based explanation. Like Chapter 4, the case study draws on extensive interviews and archival material.