The endothelium plays a crucial role in the regulation of vascular function through the release of locally important molecular effectors such as endothelium-derived relaxing factor (EDRF) and prostacyclin. Endothelial cells also regulate vascular patency and tissue perfusion by inhibiting platelet aggregation and thrombosis, suppressing intimal proliferation, and maintaining vascular tone. Disturbances of the regulatory functions of the endothelium contribute to the pathophysiology of various disease states, including cardiovascular disease and stroke. Most studies focused on endothelial control of vasomotion and, in particular, on the action of EDRF; many studies have also emphasised that altered endothelial control of fibrinolysis and intimal growth influence the clinical expression of atherothrombotic disease. Importantly, understanding the pathophysiological role of endothelial dysfunction may lead to new therapeutic approaches for disease states caused by vascular disease.