Cardiac surgery, both adult and pediatric, has developed very rapidly and impressively over the past 7 decades. Pediatric cardiac surgery, in particular, has revolutionized the management of babies born with congenital heart disease such that now most patients reach adult life and lead comfortable lives. However, these patients are at risk of cerebral lesions, which may be due to perioperative factors, such as side effects of cardiopulmonary bypass and/or anesthesia, and non-perioperative factors such as chromosomal anomalies (common in children with congenital heart disease), the timing of surgery, number of days on the intensive care unit, length of hospitalization and other hospitalizations in the first year of life. The risk of cerebral lesions is particularly relevant to pediatric cardiac surgery given that cerebral metabolism is about 30% higher in neonates, infants and young children compared to adults, which renders their brain more susceptible to ischemic/hypoxic injury. This issue has been a major concern throughout the history of cardiac surgery such that many preventive measures have been implemented over the years. These measures, however, have had only a modest impact and cerebral lesions continue to be a major concern. This is the subject of this review article, which aims to outline these protective measures, offer possible explanations of why these have not resolved the issue, and suggest possible actions that ought to be taken now.