From a global perspective, the large and diverse African population is disproportionately affected by cardiovascular disease (CVD). The historical balance between communicable and noncommunicable pathways to CVD in different African regions is dependent on external factors over the life course and at a societal level. The future risk of noncommunicable forms of CVD (predominantly driven by increased rates of hypertension, smoking, and obesity) is a growing public health concern. The incidence of previously rare forms of CVD such as coronary artery disease will increase, in concert with historically prevalent forms of disease, such as rheumatic heart disease, that are yet to be optimally prevented or treated. The success of any strategies designed to reduce the evolving and increasing burden of CVD across the heterogeneous communities living on the African continent will be dependent upon accurate and up-to-date epidemiological data on the cardiovascular profile of every major populace and region. In this Review, we provide a contemporary picture of the epidemiology of CVD in Africa, highlight key regional discrepancies among populations, and emphasize what is currently known and, more importantly, what is still unknown about the CVD burden among the >1 billion people living on the continent.