Humans have understood the importance of climate to human health since ancient times. In some cases, the connections appear to be obvious: a flood can cause drownings, a drought can lead to crop failure and hunger, and temperature extremes pose a risk of exposure. In other cases, the connections are veiled by complex or unobserved processes, such that the influence of climate on a disease epidemic or a conflict can be difficult to diagnose. In reality, however, all climate impacts on health are mediated by some combination of natural and human dynamics that cause individuals or populations to be vulnerable to the effects of a variable or changing climate. Understanding and managing negative health impacts of climate is a global challenge. The challenge is greater in regions with high poverty and weak institutions, however, and Africa is a continent where the health burden of climate is particularly acute. Observed climate variability in the modern era has been associated with widespread food insecurity, significant epidemics of infectious disease, and loss of life and livelihoods to climate extremes. Anthropogenic climate change is a further stress that has the potential to increase malnutrition, alter the distribution of diseases, and bring more frequent hydrological and temperature extremes to many regions across the continent. Skillful early warning systems and informed climate change adaptation strategies have the potential to enhance resilience to short-term climate variability and to buffer against negative impacts of climate change. But effective warnings and projections require both scientific and institutional capacity to address complex processes that are mediated by physical, ecological, and societal systems. Here the state of understanding climate impacts on health in Africa is summarized through a selective review that focuses on food security, infectious disease, and extreme events. The potential to apply scientific understanding to early warning and climate change projection is also considered.