Respiratory morbidity, particularly chronic lung disease (CLD), remains a major cause of long-term morbidity and mortality for preterm infants. Although surfactant replacement has decreased acute respiratory morbidity and mortality, it has not reduced the incidence of CLD. A number of other approaches, including antenatal thyrotropin releasing hormone in conjunction with corticosteroids, postnatal steroid administration, as well as administration of Vitamin E, diuretics, and bronchodilators, have not resulted in clinically important decreases in CLD. Infants with the most severe CLD go on to develop findings suggestive of pulmonary hypertension with cor pulmonale. There is preliminary evidence in the preterm infant with severe chronic lung disease that low-dose inhaled nitric oxide may significantly attenuate the disease and decrease mortality.