Maintenance of normal blood glucose is important for survival. In particular, brain function is dependent on circulating glucose. In health, a series of powerful counterregulatory defences operate to prevent/ limit hypoglycaemia. These defences are altered to varying degrees in diabetes and in particular, a subset of people with diabetes can develop profound deficits in these defences placing them at increased risk of suffering episodes of severe hypoglycaemia. Brain is an important controller of glucose homeostasis and developments in molecular techniques have allowed the neurocircuitry of a number of important centrally-controlled homeostatic processes such as energy balance, thirst and thermoregulation to be defined. This review describes how some of these advances have allowed a better understanding of the neuronal/ brain ensembles which help protect against hypoglycaemia.