Every year in the United States approximately 40,000 infants are born with congenital heart disease. Several of these infants require corrective or palliative surgery in the neonatal period. Mortality rates after cardiac surgery are highest amongst neonates, particularly those born prematurely. There are several reasons for the increased surgical mortality risk in neonates. This review outlines these risks, with particular emphasis on the relative immaturity of the organ systems in the term and preterm neonate.