Epidemiologic data clearly show that men and women with higher levels of physical activity have lower rates of cardiovascular disease. While the precise biologic mechanisms for this relation have not been elucidated completely, several plausible mechanisms involving traditional and novel cardiovascular risk factors have been described. In line with the 2008 federal guidelines for physical activity, the available evidence indicates that 150 min.wk(-1) of moderate-intensity aerobic activity, or the equivalent in vigorous, or moderate plus vigorous activities, is sufficient to reduce risk. There is a dose-response relation in that additional amounts of physical activity exceeding this level are associated with additional reductions in cardiovascular disease risk, supporting the 2008 federal guidelines, which further recommend 300 min.wk(-1) of moderate-intensity aerobic activity, or the equivalent in vigorous, or moderate plus vigorous activities, for additional health benefits. Among patients with established coronary artery disease, physical activity also reduces all-cause and cardiovascular disease mortality rates.