Neonatal hypoglycemia is particularly dangerous for the brain when it is symptomatic or/and recurrent. In order to avoid symptomatic hypoglycemia a compensatory production of ketone bodies is required since they are actively taken up by the neonatal brain. Recurrent hypoglycemia can be avoided by stimulation of neonatal gluconeogenesis which is limited by glucose infusion and/or insulin secretion. Lipid administration induces a hyperglycemic response which is explained by a stimulation of gluconeogenesis. It also results in ketogenesis which provides the compensatory factors of hypoglycemia and which seems to be linked to gluconeogenesis. We therefore suggest that the best way to prevent neonatal hypoglycemia is achieved by supplementing the neonate with lipids and especially medium chain triglycerides.