Much of the evidence linking a sedentary way of life to morbidity and mortality has been derived from relatively healthy populations, but there are data on the effects of physical activity in individuals with health problems or with risk factors for chronic disease. Clinicians, and often the general public, frequently consider the primary value of physical activity as the contribution it makes to control of these other risk factors. This approach underestimates the value of physical activity in the prevention and treatment of numerous chronic health conditions. There is a steep inverse gradient of morbidity and mortality across categories of cardiorespiratory fitness and physical activity in all subgroups—women and men who are middle-aged or older, obese or normal weight, or healthy or unhealthy. The overall death rates vary by these subgroups, older individuals obviously have higher death rates than younger persons, but the pattern of association of fitness or activity to mortality is comparable for the various population subgroups. In fact, fit individuals with another risk factor often have lower death rates than unfit individuals without the risk factor. Regular physical activity and moderate to high levels of cardiorespiratory fitness provide protection against numerous health problems and inactivity should be given increased attention by physicians and other health care professionals. Recent research on how to use cognitive and behavioral strategies to help sedentary individuals become more physically active has shown promising results. Exercise Is Medicine is a global initiative to address how to implement physical activity into clinical practice, and thereby help more patients improve their health.