One of the most challenging applications of cardiopulmonary bypass is corrective cardiac surgery in the neonate. The small size and high metabolic demand of these patients require miniaturized but efficient equipment. Even with the most advanced components, the volume required to prime the perfusion circuit is typically more than twice the blood volume of a neonate. Neonates have limited cardiac and pulmonary reserves and, therefore, great care is required to preserve those organs that have often already been subjected to hypoxemia, congestive heart failure, or low cardiac output prior to surgery. There is a tendency toward extravascular movement of fluids in newborns subjected to bypass that can adversely affect outcome. Careful monitoring and precise management of perfusion are essential to a successful procedure and optimal recovery of these patients.