Hyperinsulinemic hypoglycemia (HH) is fairly common in neonates, particularly those born to diabetic mothers and those who are either large or small for gestational age. Immediate management of the disease focuses on achieving normoglycemia through frequent high-calorie feedings and/or intravenous glucose administration. Glucagon may be used for unstable infants in whom intravenous access cannot be obtained and enteral feedings cannot be administered. HH that persists despite these interventions should raise concern for congenital hyperinsulinism (CHI), prompting clinicians to perform a thorough evaluation. CHI consists of a group of genetic disorders in which inappropriate insulin secretion results in persistent hypoglycemia. Defects can occur in the various genes that regulate the pathway for insulin secretion in the pancreatic β-cells. Pharmacologic therapies are used for long-term management of the disease coupled with either curative or therapeutic surgical intervention. Because of the developing brain's high demand for glucose, these infants are at increased risk for hypoglycemic brain injury. This review will describe the pathogenesis of CHI, outlining the more common genetic mutations and associated syndromes. We will also discuss the clinical presentation, diagnosis, and management of CHI while providing insight into the overall prognosis.