Sitaxsentan is the first oral endothelin receptor antagonist (ETRA) with high selectivity for the endothelin-A (ETA) receptor to be approved for clinical use by regulatory agencies in Europe for the treatment of pulmonary arterial hypertension (PAH). Clinical trials have shown it to be well tolerated and to improve exercise tolerance, functional class and pulmonary hemodynamics in PAH, results which appear to be at least as good as those for the mixed ETRA bosentan. Importantly, compared to bosentan, sitaxsentan has a lower incidence of liver toxicity and no interaction with sildenafil, a drug commonly used in the management of PAH. Furthermore, there is increasing evidence to suggest that ETRAs may play an important role in the future management of a wide variety of other conditions, from hypertension and renal disease to connective tissue disease and cancer. In some of these conditions, ETA selectivity may be an advantage. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.