Endothelins are endothelial peptides, the properties of which have been investigated for over 25 years. They play a special role in the pathophysiology of many diseases of the cardiovascular system. Endothelin-1, which is the most explored one, is a potent vasoconstrictor. It increases renal water and sodium excretion, augments cell growth and proliferation and has proinflammatory activity, by intensifying the production of reactive oxygen and nitrogen species (ROS and RNS). ET-1 takes part in the progression of such diseases as hypertension, atherosclerosis, heart and renal failure. The physio- and pathological effects of endothelins are mediated through ETA and ETB receptors. Blocking these receptors, in particular the ETA receptor, can prevent negative effects of endothelins. Long-term efforts to create drugs which act like that have brought relevant results. Endothelin receptor antagonists (ERA) are a new class of medicines, which are indicated in the treatment of pulmonary arterial hypertension. There are also optimistic results of trials with ERA administered in other disorders. On the basis of these data we may conclude that there will be more indications for this group of drugs. This review discusses properties and new research directions of ERA registered in pharmacotherapy.