Endothelin (ET-1) is a potent vasoconstrictor and smooth muscle mitogen that mediates its effects through activation of ET-A and ET-B receptors. Pulmonary arterial hypertension (PAH) encompasses a heterogeneous group of disorders characterised by inappropriate overactivation of the ET system. There is clear evidence that strategies that block both ET receptors are associated with clinical improvement in PAH. However, there are theoretical physiological advantages to treatments that specifically inhibit only the ET-A receptor. Sitaxsentan is an orally active selective ET-A receptor antagonist that in recent clinical trials has demonstrated improvements in exercise capacity, functional class and haemodynamics in PAH patients with modified New York Heart Association class II, III and IV symptoms.