Almost 30 years ago, the American Academy of Pediatrics Committee on Fetus and Newborn coauthored a policy statement strongly advocating for the use of anaesthesia in all neonates stating ‘local or systemic pharmacologic agents now available permit relatively safe administration of anesthesia or analgesia to neonates undergoing surgical procedures and that such administration is indicated according to the usual guidelines for the administration of anesthesia to high-risk, potentially unstable patients’. With current techniques and advanced monitoring, preterm and full-term infants routinely undergo surgical procedures under general anaesthesia to repair congenital defects that were lethal in years past. Recent research in immature animal models, however, has shown evidence of enhanced neuroapoptosis and other signs of neurotoxicity with all of the currently used anaesthetic agents. There is also increasing concern about the potential adverse effects of perioperative hypotension and hypocapnia on neurocognitive development in infants. This review outlines the most recent animal and human evidence regarding the effects of general anaesthesia and anaesthetic-related haemodynamic changes on the developing brain of newborns.