Acute hypoglycaemia impairs cerebral function, and available data indicate that cognitive performance becomes impaired at a blood glucose level of 2.6-3.0 mmol/l in healthy subjects. Methodological problems limit comparisons between studies, but in general complex tasks are more sensitive to hypoglycaemia than simple tasks, and some cognitive abilities are completely abolished. The onset of hypoglycaemic cognitive dysfunction is immediate, but recovery may be considerably delayed. There is persuasive evidence of adaptation to hypoglycaemia, partly due to increased brain glucose uptake capacity, although other mechanisms may exist. Patients who are exposed to chronic or recurrent hypoglycaemia become remarkably tolerant to the state, but this is insufficient to prevent severe hypoglycaemia with neuroglycopenic decompensation, probably because symptomatic and counterregulatory responses adapt even more. During experimental hypoglycaemia, administration of non-glucose cerebral fuels preserves cognitive function. However, little progress has been made as yet towards protecting cognitive function during hypoglycaemia in clinical practice. The chronic effects of recurrent hypoglycaemia remain contentious. There are numerous case reports of hypoglycaemic brain damage and of cognitive deterioration attributed to repeated severe hypoglycaemia. The major prospective studies, including the Diabetes Control and Complications Trial, did not report cognitive declines in intensively treated patients, but had unrepresentative study populations and may have been too short to detect such effects. Structural and functional brain changes are not only associated with recurrent severe hypoglycaemia, but also with hyperglycaemia and early disease onset and may in part be due to hyperglycaemic microvascular disease. Children may be more prone to acute metabolic insults, and there is evidence of developmental disadvantage associated with hypoglycaemic episodes.