1. There is an ever increasing volume of evidence implicating endothelin-1 and its isoforms in a range of disease processes. These include asthma, pulmonary and essential systemic hypertension, cardiac failure and uterine dysfunction. 2. However, it is also important to realize that the endothelins play an obligatory role in normal cellular proliferation, repair and tissue development. 3. The present brief review focuses on some of the physiological and pathophysiological mediator roles of the endothelins and provides a sketch of the receptor systems and some of the signal transduction pathways that are now known to operate following receptor activation. 4. Importantly, it is now clear that the endothelins, their receptors and synthesis and degradation pathways offer potentially important therapeutic targets.