Respiratory failure is the leading cause of death in the neonatal period. The anatomic and functional basis for this, particularly in full-term infants, most often is persistent pulmonary hypertension of the neonate (PPHN). This condition is reversible but can cause very severe and unrelenting respiratory failure and ultimate death when uncontrolled. Recent technologic advances have expanded the scope of therapy available for PPHN, resulting in increasing therapeutic success for these critically ill infants. This article reviews the anatomic and functional anomalies of PPHN, as well as the methods of diagnosis and discusses current treatment.