Portopulmonary hypertension (PPHT) is defined as precapillary pulmonary hypertension accompanied by hepatic disease or portal hypertension. Pulmonary hypertension results from excessive pulmonary vascular remodeling and vasoconstriction. These histological alterations have been indistinguishable from those of other forms of pulmonary arterial hypertension. Factors involved in the pathogenesis of PPHT include volume overload, hyperdynamic circulation, and circulating vasoactive mediators. The disorder has a substantial impact on survival and requires focused treatment. Liver transplantation in patients with moderate to severe PPHT is associated with a significantly reduced survival rate. The best medical treatment for patients with PPHT is controversial; most authors currently regard continuous intravenous application of prostacyclin as the treatment of choice for patients with severe PPHT. There is only very limited reported experience with inhaled prostacyclin or its analog, iloprost. Increasing evidence of the efficacy of the endothelin-receptor antagonist bosentan and of the phosphodiesterase-5 inhibitor sildenafil is emerging in highly selected patients with PPHT. In the future, a combination therapy of the above-mentioned agents might become a therapeutic option. Other agents such as beta-blockers seem to be harmful to patients with moderate to severe portopulmonary hypertension. Up-to-date, randomized, double-blind, controlled clinical trials are lacking and are needed urgently.