Primary and primordial prevention of cardiovascular disease (CVD) requires not only identification of risk factors, but also appropriate and timely therapy. In order to prevent the expected increase in prevalence of CVD, it is essential that clinicians are aware of behavioral cardiovascular risk factors. A basic review is critical to clarify the difference between physical activity and fitness, as well as to discuss the role each plays in cardiovascular outcomes. We discuss observational epidemiological studies and randomized control trials that have examined the effect of physical activity and cardiorespiratory fitness on CVD.