Pulmonary arterial hypertension (PAH) is a severe disease with marked morbidity and mortality for which therapeutic strategies have been limited. Basic research in vascular biology has implicated endothelin-1 (ET-1) and its receptors (ET(A) and ET(B)) in diverse preclinical models of PAH, and ET-1 has been shown to contribute significantly to PAH in human patients. Despite the complexity of roles of the ET receptors in the development or reversal of PAH in the laboratory, the introduction of endothelin receptor antagonists (ETRAs) to clinical medicine has substantially expanded our therapeutic approach toward severe PAH. This article briefly reviews preclinical data and the current status of ETRAs in the clinical management of PAH.