The improvements in care of children with heart disease have resulted in a major decrease in mortality and increased attention to adverse events and quality of survival. There is important neurological morbidity in children with congenital heart disease. Some problems such as stroke or seizure may be immediately apparent, but others, such as learning disability and motor delay emerge over time. The etiology is multifactorial and includes genetic, procedural and social causes. Only some factors are modifiable. Over the last decade, evidence has been presented that anesthetic drugs may be a potential cause of CNS morbidity. Neonates and infants may be particularly vulnerable to this. The purpose of this article is to describe the multiple known causes of neurodevelopmental impairment in children with heart disease, including anesthetic agents, and to explore the relationship between congenital heart disease and its treatment in this regard.