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In January 2010 PLOS Medicine launched a four-part series examining the ways in which global health institutions and arrangements are changing and evolving. The series aims to stimulate debate, encourage further case studies, and provide insights into general principles for the improvement of the global health system. In the introductory article, Nicole A. Szlezák and colleagues analyze the changing relationships between the new and old actors in global health. In the second paper, Julio Frenk discusses the crucial role of national health systems in making progress in global health. Gerald T. Keusch and colleagues examine institutional arrangements for malaria research in the third article in the series. And in the fourth and final article Suerie Moon and colleagues propose future actions to strengthen global health institutions.