Diagnosis of portopulmonary hypertension (PoPH), is challenging because of the multitude of cardiac and pulmonary diseases that cosegregate with advanced liver disease. PoPH is unique in that its natural history is not wholly dependent on portal hypertension. Despite a dearth of randomized, prospective data, an ever-expanding clinical experience shows that patients with PoPH benefit from therapy with PAH-specific medications. Because of high perioperative mortality, transplantation should be avoided in those patients who have severe PoPH that is refractory to medical therapy. This article reviews the pathophysiology and pathogenesis of PoPH and discusses approaches to diagnosis and management.