The importance of strengthening health systems has gained increased attention in recent years, and there have been renewed calls for a focus on health systems as part and parcel of meeting the health related Millennium Development Goals. Despite the growing focus on health systems, the largest global health initiatives -- suchas PEPFAR, PMI, the Global Fund to Fight AIDS, TB, and Malaria, and GAVI -- continue to have a disease specific focus. The divergence in opinion on what constitutes health systems strengthening and the scarcity of rigorous evaluations of various approaches undermine efforts to focus on health systems as a means of improving population health. In response to this challenge, the Doris DukeCharitable Foundation (DDCF) launched the African Health Initiative (AHI) to catalyze significant advances instrengthening health systems by supporting Population Health and Implementation Training (PHIT) Partnerships in five diverse sub-Saharan African contexts. Each Partnership is implementing and evaluating an innovative project designed to address key health systems constraints and improve service delivery and health outcomes. This article is a preface to a series of reports.