Congenital hyperinsulinism (CHI), previously termed persistent hyperinsulinemic hyperglycemia of infancy (PHHI), is a spectrum of conditions characterized by profound hypoglycemia in the presence of inappropriately high insulin secretion.1 , 2 Although rare overall, CHI is a significant cause of hypoglycaemic brain injury in the newborn1 and subsequent mental retardation,3 and therefore, all those involved in the medical and surgical management of neonates need to be familiar with this condition so that the diagnosis can be made promptly, and early treatment implemented. This chapter provides an overview of the etiology, clinical presentation, diagnosis, and management of CHI to facilitate this.