The fetus is completely dependent on mother for glucose and other nutrient transfer across the placenta. At birth, when the maternal supply is discontinued, the neonate must adjust to an independent existence. The changes in the neonate's glucose homeostasis during this transition to the extrauterine environment are influenced by the mother's metabolism and intrinsic fetal and placental problems. Maturation of carbohydrate homeostasis results from a balance between substrate availability and coordination of developing hormonal, enzymatic, and neural systems. These mechanisms may not be fully developed in neonates, so the neonate is vulnerable to carbohydrate disequilibrium resulting in damage to the central nervous system. Hypoglycemia is a relatively common metabolic problem seen during newborn care. However its definition, management and long term sequalae remain controversial. Hyporglycemia occurs frequently as a transient disorder with excellent prognosis. It also may persist and recur and cause permanent neurological complications. Although the key to effective treatment of hypoglycemia is diagnostic specific, the maintenance of euglycemia is critical to the preservation of central nervous system function. This article discusses physiology of perinatal glucose homeostasis, focusing on evaluation and treatment of hypoglycemia.