Advances in both surgical techniques and perioperative care have led to improved survival outcomes in infants and children undergoing surgery for complex congenital heart disease. An awareness is emerging that early and late neurological morbidities complicate the outcome of these operations. Adverse neurological outcomes after neonatal and infant cardiac surgery are related to both fixed and modifiable mechanisms. Fixed factors include many variables specific to the individual patient, including genetic predisposition, gender, race, socioeconomic status, and in utero central nervous system development. Modifiable factors include not only intraoperative variables (cardiopulmonary bypass, deep hypothermic circulatory arrest, and hemodilution) but also such variables as hypoxemia, hypotension, and low cardiac output. The purpose of this review is to examine these mechanisms as they relate to available outcome data.