Despite extensive literature on the subject, hypoglycemia in infants and children remains a puzzling yet urgent diagnostic and therapeutic challenge. When the patient presents with vague symptoms, pediatricians may find it hard to determine whether an extensive work-up is indicated, such as a diagnostic fast. In children, conditions that cause hypoglycemia are often complex, diverse, and unique; therefore, evaluation and management of the hypoglycemic child requires a substantial knowledge of all physiologic mechanisms that maintain euglycemia. This article reviews the different aspects of glucose homeostasis in infants and children, the various causes of hypoglycemia, and the adverse effect of low blood glucose on the central nervous system. It also attempts to give a practical approach to the management and treatment of hypoglycemic disorders in childhood.