During the past 10 years, it has become obvious that endothelium regulates vasomotion, modulates hemostasis, influences vascular permeability, and controls blood vessel growth. The role of endothelium in modulating vasomotor tone is mediated by the releasing of a number of potent vasoactive compounds, including endothelium-derived relaxing factors (one of which is either nitric oxide or a compound that releases nitric oxide), vasoactive prostaglandins, endothelium-derived hyperpolarizing factor, and a number of constricting factors (such as thromboxane A2, endothelin, superoxide anion, L-arginine-dependent products etc.). This role of the endothelium is dramatically changed by several disease processes, including diabetes mellitus, cerebrovascular disease, and so on. Abnormalities of endothelial regulation of vascular tone may contribute to a number of clinical syndromes, including atherosclerosis, hypertension, septic shock syndrome, and many others. Endothelium dysfunction, characterized by altered synthesis or release of these relaxing factors along with maintained or facilitated synthesis or release of contracting factors, can lead to various pathological conditions such as thrombosis, vasospasm, and hypertension. Better understanding of the exact nature of endothelial dysfunction, including the role played by endothelium-derived vasoactive factors, may provide a basis for novel therapies in these vasculopathies.