A plethora of epidemiologic evidence from large studies supports unequivocally an inverse, independent, and graded association between volume of physical activity, health, and cardiovascular and overall mortality. This association is evident in apparently healthy individuals, patients with hypertension, type 2 diabetes mellitus, and cardiovascular disease, regardless of body weight. Moreover, the degree of risk associated with physical inactivity is similar to, and in some cases even stronger than, the more traditional cardiovascular risk factors. The exercise-induced health benefits are in part related to favorable modulations of cardiovascular risk factors observed by increased physical activity or structured exercise programs. Although the independent contribution of the exercise components, intensity, duration, and frequency to the reduction of mortality risk is not clear, it is well accepted that an exercise volume threshold defined at caloric expenditure of approximately 1,000 Kcal per week appears to be necessary for significant reduction in mortality risk. Further reductions in risk are observed with higher volumes of energy expenditure. Physical exertion is also associated with a relatively low and transient increase in risk for cardiac events. This risk is significantly higher for older and sedentary individuals. Therefore, such individuals should consult their physician prior to engaging in exercise. “Walking is man’s best medicine” Hippocrates 1. Introduction Over 2,500 year ago, Hippocrates noted the potential health benefits of daily exercise of moderate intensity such as a simple walk. In the last six decades, and since the landmark work by Morris and coworkers [1], the plethora of epidemiologic evidence accumulated supports unequivocally an inverse, independent, and graded association between physical activity, health, and cardiovascular and overall mortality in apparently healthy individuals [2–22] and in patients with documented cardiovascular disease [9]. The exercise-induced health benefits are in part related to favorable modulations of cardiovascular risk factors that have been observed with increased physical activity patterns or structured exercise programs [10]. Most recently the discovery that skeletal muscles are capable of communicating with other tissues by the release of myokines into the circulation aids to our understanding of the exercise-induced health benefits on the molecular level. More specifically, Bostr？m and colleagues [23] identified a new hormone irisin, named after the ancient Greek goddess of the rainbow and
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