Rapid evaluation of a neonate who is cyanotic and in respiratory distress is essential for achieving a good outcome. Persistent pulmonary hypertension of the newborn (PPHN) can be a primary cause or a contributing factor to respiratory failure, particularly in neonates born at 34 weeks or more of gestation. PPHN represents a failure of normal postnatal adaptation that occurs at birth in the pulmonary circulation. Rapid advances in therapy in recent years have led to a remarkable decrease in mortality for the affected infants. Infants who survive PPHN are at significant risk for long-term hearing and neurodevelopmental impairments, however. This review focuses on the diagnosis, recent advances in management, and recommendations for the long-term follow-up of infants who have PPHN.