Intercellular signaling is an important factor in cardiovascular regulation and the development of disease. The endothelins (ETs) are a recently described family of signaling peptides that appear to be important in cardiovascular regulation. Initial studies showed ET to be a potent vasoconstrictor of vascular smooth muscle. Subsequently, ET binding and activity have been demonstrated in a wide variety of tissues, including cardiac, venular, adrenal, and neural. Numerous studies have implicated the ETs in cardiovascular diseases such as hypertension, heart failure, and atherosclerosis. This article briefly reviews ET signaling pathways and the roles ET may play in cardiovascular regulation and disease.