The possible involvement of endothelins in a variety of diseases has attracted the attention of many pharmacologists in search of a navel therapeutic approach. The rapid development of endothelin research has resulted in the molecular characterization and pharmacological recognition of ET(A) and ET(B) receptors, and in the development of compounds selective for these receptors. However, the characterization of receptors in various assays has shown that a number of effects are mediated by receptors that do not fit the present criteria for ET(A) or ET(B) receptors. In this article, Willem Bax and Pramod Saxena address endothelin receptors in general, and atypical receptors in particular.