There is an increasing concern regarding the risk of anaesthetic neurotoxicity in children. Numerous animal and in vitro studies have demonstrated that general anaesthetics cause a variety of potentially harmful effects on the developing brain. An increased level of neuronal apoptosis is one such effect. In some studies, exposed animals have experienced long-lasting neurobehavioural changes. These effects occur at very specific stages of development and are dose-dependent. There are several plausible mechanisms for these deleterious effects; however, the exact mechanism remains unclear. Most importantly, histological and behavioral effects have been demonstrated in non-human primates. Human research evaluating the long-term effects of anaesthesia on brain development is limited and, to date, has been limited to retrospective observational cohort studies. The results of these studies have not been consistent, with some demonstrating an association between surgery and adverse neurobehavioral outcome and others showing no association. Furthermore, these cohort studies have numerous weaknesses and limitations. An ongoing randomized clinical trial aims to provide clear evidence regarding the clinical safety of anesthetics up to 1 h in neonates and older children.