1. It has been generally accepted that regular physical activity is associated with beneficial effects on the cardiovascular system. In fact, the idea that exercise maintains cardiovascular health is evident by the direct links between a sedentary lifestyle and the risk of cardiovascular and other disease states. 2. Cardiovascular diseases, such as hypertension and heart failure, are often associated with sympathetic nervous system (SNS) overactivity. Conversely, exercise has been shown to reduce hypertension and decrease elevated SNS activity. In addition, there is evidence that exercise may reduce resting blood pressure and sympathetic outflow in normal individuals. 3. Although somewhat controversial in humans, evidence from animal studies also indicates that exercise training reduces baroreflex-mediated and other forms of sympathoexcitation in normal individuals. Collectively, these data are consistent with the hypothesis that physical activity may decrease, and physical inactivity may increase, the incidence of cardiovascular disease via alterations in SNS activity. Despite the important clinical implications of this possibility, the mechanisms by which exercise alters control of SNS activity remain to be fully elucidated. 4. Recent evidence suggests that central nervous system (CNS) plasticity occurs under a variety of conditions, including varying levels of physical activity. The purpose of the present brief review is to provide evidence that changes within the CNS contribute importantly to altered regulation of the SNS observed following exercise training. The primary hypothesis is that physical activity versus inactivity produces plasticity within neural networks that regulate SNS activity. This hypothesis is supported by published and preliminary data that suggest that exercise training may reduce sympathoexcitation by reducing activation of neurons within cardiovascular regions of the brain. These mechanisms are likely to be important in disease states of sympathetic overactivity and in normal healthy individuals whose risk of cardiovascular disease is reduced by leading an active versus sedentary lifestyle.