The endothelins (ETs) are potent vasoactive peptides that appear to be involved in diverse biological actions, for example, contraction, neuromodulation, and neurotransmission, as well as in various pathophysiological conditions, such as renal and heart failure. The diversity of actions of ETs may be explained in terms of (1) the existence of several receptor subtypes and (2) the activation of different signal transduction pathways. This review summarizes the state of the art in this intensively studied field, with particular focus on structural aspects, receptor heterogeneity, coupling of receptors to G-proteins, and signal transduction mechanisms mediated by the activation of ET-receptors.