This article highlights research supporting the concept that increased physical activity and cardiorespiratory fitness attenuate risk of cardiovascular disease, type 2 diabetes, and the metabolic syndrome. Increased activity and fitness also attenuate risk of developing cardiovascular disease in persons who have type 2 diabetes or the metabolic syndrome. Although controversial, relationships between physical activity/physical fitness and type 2 diabetes/metabolic syndrome are largely independent of body weight. Thus, physical inactivity and poor cardiorespiratory fitness are not only important determinants of cardiovascular and metabolic diseases, but they can also be considered common features of these conditions, much like traditional risk factors such as obesity and insulin resistance.