Pulmonary arterial hypertension frequently occurs secondary to common cardiopulmonary diseases, and more rarely as a primary condition. Observations in animals and man have suggested genetic influences underlying the susceptibility to pulmonary hypertension. A gene underlying many cases of familial and apparently sporadic cases of primary pulmonary hypertension has now been identified, and a genetic approach to hypoxia-induced pulmonary hypertension promises to reveal new insights into the unique nature of the pulmonary circulation. The exploration of potential candidate genes influencing susceptibility and the identification of new genes promise new therapeutic approaches to the treatment of pulmonary hypertension.