Information on exposure to, and health effects of, cardiovascular disease (CVD) risk factors is needed to develop effective strategies to prevent CVD events and deaths. Here, we provide an overview of the data and evidence on worldwide exposures to CVD risk factors and the associated health effects. Global comparative risk assessment studies have estimated that hundreds of thousands or millions of CVD deaths are attributable to established CVD risk factors (high blood pressure and serum cholesterol, smoking, and high blood glucose), high body mass index, harmful alcohol use, some dietary and environmental exposures, and physical inactivity. The established risk factors plus body mass index are collectively responsible for ≈9.7 million annual CVD deaths, with high blood pressure accounting for more CVD deaths than any other risk factor. Age-standardized CVD death rates attributable to established risk factors plus high body mass index are lowest in high-income countries, followed by Latin America and the Caribbean; they are highest in the region of central and eastern Europe and central Asia. However, estimates of the health effects of CVD risk factors are highly uncertain because there are insufficient population-based data on exposure to most CVD risk factors and because the magnitudes of their effects on CVDs in observational studies are likely to be biased. We identify directions for research and surveillance to better estimate the effects of CVD risk factors and policy options for reducing CVD burden by modifying preventable risk factors.