Endothelins are peptides with powerful vasoconstrictor and mitogenic properties. It has become evident that endothelins are involved in many regulatory mechanisms of the circulation in which they have a modulating role both in short and in long term. However, in many cases it remains unclear whether the alteration of the endothelin metabolism is a primary pathology or a secondary phenomenon. The synthesis of endothelin receptor antagonists and animal models with altered endothelin metabolism have opened a new era of endothelin research that will allow insight into the mechanisms of endothelin-action and eventually might lead to new therapeutic concepts. This review discusses the evidence both in favor and against pathogenic effects of endothelins in cardiovascular disease.