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When the normal cardiopulmonary transition fails to occur, the result is persistent pulmonary hypertension of the newborn. Severe persistent pulmonary hypertension of the newborn is estimated to occur in 2 per 1000 live-born term infants, and some degree of pulmonary hypertension complicates the course of >10% of all neonates with respiratory failure. This review article discusses the vascular abnormalities that are associated with neonatal pulmonary hypertension, including recognition of its role in severe bronchopulmonary dysplasia in preterm infants. A systematic review of the evidence for common therapies including inhaled nitric oxide, high-frequency ventilation, surfactant, and extracorporeal life support is included. Finally, this field is rapidly evolving, and the rationale for promising new treatment approaches is reviewed, including inhibition of phosphodiesterases and scavengers of reactive oxygen species.