Endothelial dysfunction is one of the hallmarks of cardiovascular disease and serves as a prognostic marker for forecasting the development and outcome of the disease process. Current pharmacological treatment strategies only incompletely repair endothelial dysfunction whereas exercise training corrects this dysfunction, primarily due to improved production and/or bioavailability of nitric oxide, the main endothelium-derived vasodilator. This type of treatment also improves the function of healthy endothelium. The focus of this review is to discuss the underlying biological factors involved in improved endothelial function after exercise training in healthy individuals as well as those with cardiovascular disease or a metabolic syndrome. The ability to sustain the bioavailability of nitric oxide (NO) in the endothelium is probably the most important factor in restoring normal endothelial function by exercise training.