Sedentary lifestyle along with high blood pressure, abnormal values for blood lipids, smoking, and obesity are recognized risk factors for cardiovascular diseases and for many other chronic diseases, such as diabetes, osteoporosis, breast and colon cancer. Several studies conducted on large cohort of individuals have documented the protective effects of physical activity for both vascular and nonvascular syndromes. Exercise training is an integral part of cardiac rehabilitation, a complex therapeutic approach, effective both in young and elderly patients. Despite the number of evidences underling the benefits associated with physical fitness, the cardiac rehabilitation is still an underused medical resource. The molecular mechanism behind physical activity protective effect is presently unresolved, and further studies are also needed to establish the best protocol in terms of specificity, volume and duration of the training.