Article published in PLoS Medicine 2013;10(3):e1001405, 19 March 2013. Immunisation is amongst the most cost-effective public health interventions for reducing global child morbidity and mortality. The global effort to use vaccination as a public health intervention began when the World Health Organization (WHO) launched the Expanded Programme on Immunization (EPI) in 1974. Over the years there have been several international efforts to increase EPI coverage, including Universal Childhood Immunisation; the Global Alliance for Vaccines and Immunisation (GAVI); Millennium Development Goals (MDGs); the Global Immunisation Vision and Strategy (GIVS); and most recently, the Global Vaccine Action Plan (GVAP). These initiatives, coupled with specific regional efforts such as the WHO African Region's EPI strategic plans of action for the periods 2001–2005 and 2006–2009, and the Reach Every District (RED) approach, as well as the efforts of national EPIs, have seen global coverage with three doses of the diphtheria-tetanus-pertussis vaccine by 12 months of age (DTP3) rise from 5% in 1974 to 85% in 2010. However, sub-Saharan Africa reached only 77% DTP3 coverage in 2010. Although DTP3 is an acknowledged indicator of EPI performance, it is important to understand other EPI indicators in Africa. Here, we assess immunisation systems strengthening, accelerated disease control efforts, and the introduction of new and underutilised vaccines across Africa.