Numerous epidemiological studies show that physical activity improves health and decreases cardiovascular mortality by approximately 30% across age, gender, and race/ethnicity. Regular physical activity using large muscle groups, such as walking, running, or swimming, produces cardiovascular adaptations that increase exercise capacity, endurance, and skeletal muscle strength. Habitual physical activity also prevents the development of coronary artery disease and reduces symptoms and progression in patients with established cardiovascular disease. Exercise capacity has shown to be a more powerful predictor of mortality among men than other established risk factors for cardiovascular disease. Positive and protective effects of physical activity for the cardiovascular system are mediated through the endothelium, the autonomous nervous system, the clotting/coagulation system, and in particular through anti-inflammatory effects. This article summarizes the evidence for the benefits of physical activity and exercise in the prevention and treatment of cardiovascular disease.