Salt sensitivity of blood pressure is a cardiovascular risk factor, independent of and in addition to hypertension. In essential hypertension, a conglomerate of clinical and biochemical characteristics defines a salt-sensitive phenotype. Despite extensive research on multiple natriuretic and antinatriuretic systems, there is no definitive answer yet about the major causes of salt-sensitivity, probably reflecting the complexity of salt-balance regulation. The endothelins, ubiquitous peptides first described as potent vasoconstrictors, also have vasodilator, natriuretic and antinatriuretic actions, depending on their site of generation and binding to different receptors. We review the available data on endothelin in salt-sensitive essential hypertension and conclude that abnormalities of renal endothelin may play a primary role. More importantly, the salt-sensitive patient may have blood pressure-dependency on endothelin in all states of salt balance, thus predicting that endothelin receptor blockers will have a major therapeutic role in salt-sensitive essential hypertension.