To prevent the devastating effects of hypoglycemia on the CNS of the infant, persistent infantile hypoglycemia should be recognized early and treated promptly. To avoid mental retardation, surgical intervention should not be considered as a last resort. When an insulinoma is identified at surgery, subtotal pancreatectomy is adequate in achieving normoglycemia. However, the most common cause of insulin excess in infancy appears to be islet cell hyperplasia or nesidioblastosis, both diffuse processes. In these patients, subtotal pancreatectomy is often ineffective in achieving normoglycemia. Near-total pancreatectomy, retaining the spleen and duodenum, is a safe procedure, well tolerated by infants and children, and should be considered early for the correction of hypoglycemia of infancy that is not readily controlled by medical intervention.