Coronary heart disease, the primary health problem in western life, is caused by the interaction of multiple factors. Absolute proof of the contributing role of physical inactivity is not possible owing to the complexity of the CHD problem and the infeasibility of a definitive clinical trial because of logistical and economic constraints. Despite limitations, existing epidemiologic studies strongly suggest, but fall short of proving, the concept that habitual physical exercise offers partial protection against primary or secondary events of CHD and associated mortality. However, experimental data support this hypothesis and provide evidence of possible mechanisms responsible for the protection. The available epidemiologic data also suggest that physical inactivity is probably not as potent an individual risk factor as elevated serum cholesterol levels, hypertension, and cigarette smoking, and that the protective effects of exercise may be overwhelmed by high levels of these major risk factors. On the other hand, there is some evidence that exercise may attenuate other risk factors both directly and through associated weight reduction.