There are five metabolic pathways and five hormones that maintain glucose homeostasis at all ages. They are particularly important during the transition period from the intrauterine to the extrauterine environment. Neonatal hypoglycemia has numerous causes, that can be divided into causes of transient or persistent hypoglycemia. The brain has various ways of adapting to hypoglycemia, the use of alternate fuels being an important mechanism. Hypoglycemia causes a characteristic brain pathology. Several symptoms have been attributed to hypoglycemia. Symptomatic hypoglycemia has been associated with an increased risk of adverse neurological outcome. The relationship of asymptomatic hypoglycemia with neurological outcome is still controversial, particularly if it occurs in otherwise healthy term infants. The definition of hypoglycemia is still uncertain, but there is a consensus on the levels at which action must be taken.