Endothelin-1 (ET-1) is a peptide with various biological activities, such as vasoconstriction, mitogenesis and bronchoconstriction. It has been implicated in the pathogenesis of numerous disease processes. Suppression of the production of this peptide by inhibitors of endothelin-converting enzyme-1 (ECE-1), the key enzyme in ET-1 biosynthesis, may be a therapeutic option. There are three classes of ECE-1 inhibitors: selective ECE-1 inhibitors, dual ECE-1/neutral endopeptidase (NEP) 24.11 inhibitors and triple ECE-1/NEP/angiotensin-converting enzyme inhibitors. This review will focus briefly on the endothelin system and mainly on the ECE-1 inhibitor classes, their pharmacologic effects on animal models of various diseases and published clinical studies.