Summary. The burden of cardiovascular disease (CVD), especially ischemic heart disease and stroke, varies remarkably between regions of the world, with declining rates in Europe, North America, and Australia/New Zealand, burgeoning epidemics in the former socialist economies and India, and relatively lower impact in developing regions such as sub-Saharan Africa. The basis for a prediction of a global CVD epidemic lies in the “epidemiologic transition,” in which control of infectious, parasitic, and nutritional diseases allows most of the population to reach the ages in which CVD manifests itself. In fact, CVD is already the leading cause of death not only in developed countries but, as of the mid-1990s, in developing countries as well. A variety of myths have attempted to minimize the rationale for CVD control in developing countries. In reality, CVD affects men, not only the elderly, and the rich, but rather a broad spectrum of the population. Moreover, as a cause of disability it will be a world leader by 2020. Finally, there is evidence that the epidemic can be curtailed. Projections to the year 2020 predict an expansion of the CVD epidemic to the developing world, with CVD exceeding infectious and parasitic diseases in all regions except sub-Saharan Africa. These estimates, in fact, may be conservative, because several factors may allow multiplication of risk. In utero or early childhood deprivation, the use of disposable income for deleterious health behaviors (such as tobacco and a high fat/cholesterol diet), interactions between multiple coexisting risk factors, and the interaction between newly acquired health behaviors and genes may all inflate the risk to levels above those predicted. Efforts to control CVD should invest strategically in research to understand the prevalence of, and risks associated with, CVD risk factors, as well as in studies of new risk factors, measures to prevent or modify risk, and clinical trials to demonstrate the efficacy of these interventions. In lieu of this improved research base, a number of initiatives should go forward to prevent the dissemination of risk factors, to treat risk factors appropriately in high-risk subjects, and to develop case-management strategies shown to be both efficacious and cost effective. A global epidemic of CVD in developing countries may be inevitable unless there is a better understanding of its origins, a prediction of its magnitude, and the organization of preventive and case-management strategies early enough to control it.