The origins of cholera incidence in Africa are socio-economic and environmental. Moreover, the nature of Vibrio cholerae transmission and survival presents a persistent risk of cholera. The Infectious Disease Risk Management Program (IDRM) in Mozambique confronted this in one of the recent most cholera-prevalent locations of the world. The first phase of the program suggests that recognizing the complexity of cholera is crucial to its effective management. The potential impacts of integrated and locally monitored cholera risk assessment are reduced uncertainty about the origins of epidemics, improved diarrhoeal disease control, and health security.