Cor pulmonale is right ventricular enlargement secondary to pulmonary hypertension. Although most often caused by parenchymal lung disease, derangements of the ventilatory drive, the respiratory pumping mechanism, or the pulmonary vascular bed may also result in right ventricular hypertrophy and dilatation. Arterial hypoxemia (and resultant polycythemia), hypercapnia, and respiratory acidosis all contribute to the increased afterload on the right ventricle. Diagnosis is often difficult, since pulmonary vascular disease, pulmonary hypertension, and cor pulmonale have few specific manifestations, especially early in their evolution. Treatment is primarily directed at the underlying pulmonary or ventilatory disorder, rather than at the right ventricular failure per se. Supplemental oxygen is essential to avoid hypoxia; corticosteroids, anticoagulants, vasodilators, and other specific therapies are used as indicated to treat the underlying pulmonary disorders. When medical therapies fail, lung or heart-lung transplantation has become a possibility for selected patients.