Over the coming decades, sub-Saharan Africa will face profound stresses and challenges from global climate change. Many of these will manifest as adverse health outcomes. This article uses a series of five hypothetical cases to review the climate impacts on the health and well-being of individuals and populations in sub-Saharan Africa. This approach fosters insights into the human dimensions of the risks to health, their interaction with local human ecology, and awareness of the diverse health ramifications of external environmental changes. Each case illustrates the health impact resulting from a specific environmental or social consequence of climate change, including impacts on agriculture and food security, droughts, floods, malaria, and population displacement. Whereas the article focuses on discrete manifestations of climate change, individuals will, in practice, face multiple stresses from climate change (i.e., floods and malaria) concomitant with other non-climate stressors (i.e., HIV/AIDS, globalization, etc.). These multiple sources of vulnerability must be considered when designing climate change and socioeconomic development interventions.