Physical activity has profound impacts on the vasculature in humans. Acute exercise induces immediate changes in artery function, whereas repeated episodic bouts of exercise induce chronic functional adaptation and, ultimately, structural arterial remodeling. The nature of these changes in function and structure are dependent on the characteristics of the training load and may be modulated by other factors such as exercise-induced inflammation and oxidative stress. The clinical implications of these physiological adaptations are profound. Exercise impacts on the development of atherosclerosis and on the incidence of primary and secondary cardiovascular events, including myocardial infarction and stroke. Exercise also plays a role in the amelioration of other chronic diseases that possess a vascular etiology, including diabetes and dementia. The mechanisms responsible for these effects of exercise on the vasculature are both primary and secondary in nature, in that the benefits conferred by changes in cardiovascular risk factors such as lipid profiles and blood pressure occur in concert with direct effects of arterial shear stress and mechanotransduction. From an evolutionary perspective, exercise is an essential stimulus for the maintenance of vascular health: exercise is vascular medicine.