Advances in the management of infants with congenital heart disease have lead to a striking decrease in mortality. The most dramatic impact has been in the newborn infant with complex and previously lethal heart disease. These heart lesions have become amenable to corrective procedures in the newborn period because of the development of support techniques such as low-flow cardiopulmonary bypass and deep hypothermic circulatory arrest. However, these techniques have demonstrated their own inherit risk for neurologic injury. Consequently, in recent years there has emerged a growing population of infants surviving congenital heart disease only to manifest subsequent neurologic complications originating from injury in the hemodynamically unstable preoperative period or periods of intraoperative hypoperfusion. The preservation of neurology function has emerged as the next frontier in the management of congenital heart disease. Finally, neurologic dysfunction in the newborn with cardiac disease may reflect associated brain malformations or the combined cardiac and brain manifestations of inherited metabolic disease. The clinical features and mechanisms of brain injury are discussed for these structural and metabolic cardiac diseases presenting in the newborn infant.