Hyperinsulinism is undoubtedly the most important cause of hypoglycemia in early infancy. Transient hyperinsulinism is not only well recognized in infants of diabetic mothers but also has been implicated in the prolonged hypoglycemia seen in SGA or asphyxiated newborns. Persistent hypoglycemia occurs in a group of disorders of congenital hyperinsulinism that comprise the most common cause of hypoglycemia in early infancy beyond the immediate neonatal period. Recent advances have begun to unravel specific genetic defects in this important group of disorders. Patients affected with any of the various forms of hyperinsulinism are at high risk for seizures and permanent brain damage. Therefore, efficient diagnosis and treatment are essential. The purpose of this article is to provide a practical outline of the various forms of hyperinsulinism and a logical approach to diagnosis and treatment.