Abstract Endothelin-1 (ET-1) is a vasoconstrictor, proinflammatory and proliferative endothelial cell-derived peptide that is of significant importance in the regulation of vascular function. It is involved in the development of endothelial dysfunction including important interactions with nitric oxide. The expression and functional effects of ET-1 and its receptors are markedly altered during development of cardiovascular disease. Increased production of ET-1 and its receptors mediate many pathophysiological events contributing to the development of atherosclerosis and vascular complications in diabetes mellitus. The present review focuses on the pathophysiological role of ET-1 and the potential importance of ET receptors as a therapeutic target for treatment of these conditions.