Endothelin-1 (ET-1) was originally identified as an endothelium-derived peptide with potent local constrictor and systemic pressor effects. Consequently it was implicated as a mediator in the control of systemic as well as peripheral vascular tone. The intense activity that followed the discovery of ET-1 has shown that endothelium is not the only site of synthesis nor is smooth muscle the sole target. ET-1 is capable of initiating and regulating an array of cellular responses including contraction, proliferation, synthesis of extracellular matrix proteins and induction of proto-oncogene expression. This diversity of function is paralleled by an increasing number of mediators capable of inducing synthesis of ET-1 in an ever increasing array of cell types. ET-1 is also a neuropeptide; mRNA for ET-1 has been identified by in situ hybridization in human spinal cord and dorsal root ganglia, and ET-1 was shown to modulate adrenergic neurotransmission at the neuro-effector junction. This review will highlight some of the recent advances in our understanding of the mechanisms regulating the synthesis of and cellular responses to ET-1 with particular reference to its potential role in the maintenance of cutaneous homeostasis and in the pathophysiology of cutaneous diseases.