Inhaled nitric oxide (NO) plays an important role in treating persistent pulmonary hypertension of the newborn (PPHN), which is marked by a pathologic elevation of pulmonary vascular resistance. There is good evidence that the use of inhaled NO reduces the need for extracorporeal membrane oxygenation for term babies with severe PPHN of any cause, except in those infants with congenital diaphragmatic hernia, for which a benefit has not been shown. Although reducing the need for extracorporeal membrane oxygenation is beneficial in terms of cost and morbidity, inhaled NO has not been shown to decrease mortality in any neonatal population. Inhaled NO has also been shown to improve oxygenation in premature infants, although longer-term benefits have not been consistently demonstrated. This article will review the physiology of NO, its mechanisms of action in PPHN, and examine the evidence that supports its use in term and preterm infants with pulmonary hypertension. (C) 2006 Elsevier Inc. All rights reserved.