Cardiovascular disease (CVD) and its risk factors, which are major health burdens in high-income countries, are a growing problem in developing or lower-income countries, where the vast majority of CVD now occurs. Two case-control studies, INTERHEART and INTERSTROKE, which included a majority of patients from developing countries, were seminal in identifying common risk factors explaining the vast majority of risk for acute myocardial infarction and stroke, respectively. The population-based Prospective Urban and Rural Epidemiological (PURE) study, which included > 150,000 participants, also with a majority from developing countries, found that although high-income countries were at highest cardiovascular (CV) risk, they had the lowest incidence of CVD and associated case-fatality rates, whereas patients in low-income countries had the lowest CV risk and yet the highest CVD and case-fatality rates. The PURE study also demonstrated relatively low rates of CV medicine use in high- and middle-income countries, but even lower rates in low-income countries, where these medicines were often either unavailable or unaffordable. The PURE study also demonstrated that control of CV risk factors and adherence to lifestyle modifications, although suboptimal globally, were poorest in low-income countries. Taken together, these data identify common CV risk factors requiring targeted, systematic, sustained, and effective interventions in developing countries to mitigate the emerging epidemic of CVD in these regions of the world.