A considerable number of observational and intervention studies support the role of exercise as a cornerstone in prevention and treatment of cardiovascular disease (CVD), type 2 diabetes (T2D), and the metabolic syndrome. Physical activity and cardiorespiratory fitness are also associated with reduced mortality rates among persons with CVD, T2D, and metabolic syndrome. Exercise has definite acute effects on a number of risk markers for CVD and T2D, in addition to more substantial benefits with chronic training. Both aerobic and resistance exercise have therapeutic value, largely independent of weight loss, and should be included in excise programs.