Endothelial function is critical to cardiovascular health, regulating blood vessel function through the release of vasodilators and constrictors—namely, nitric oxide—controlling redox balance, platelet activation and aggregation, leukocyte adhesion, and proliferation of vascular smooth muscle. Vascular dysfunction, characterized by impaired endothelial function, significantly increases cardiovascular disease (CVD) risk. CVD is the leading cause of death in the United States and most of the world. Advancing age is a primary risk factor; however, several health behaviors influence vascular aging. Risk factors such as poor diet, a sedentary lifestyle, and poor sleep can reduce endothelial function, even early in life. Exercise has emerged as a protective factor that can potentially confer vascular protection in the context of negative health behaviors. In this review, we seek to address the importance of endothelial function for cardiovascular health, identify key risk factors and mechanisms that contribute to endothelial dysfunction, summarize the protective effects of exercise against endothelial dysfunction (including mechanisms), and highlight key knowledge gaps and future directions.