Hypoglycemia with or without diabetes is associated with increased mortality risk in hospitalized patients. Before proceeding with investigations for hypoglycemia in those without major acute or chronic illness, there must be documentation of a low blood glucose associated with symptoms of hypoglycemia that resolve by restoring normoglycemia (Whipple’s triad). When major illness is present, laboratory glucose levels <55 mg/dl merit evaluation. Common causes of hypoglycemia in the hospital include medications, organ system failure, sepsis, endocrinopathies, and non-islet cell tumors. Rarely insulinoma- or non-insulinoma-related hyperinsulinemia or insulin like growth factor may be responsible for hypoglycemia. Laboratory evaluation, performed at the time of hypoglycemia, will help in identifying the cause of hypoglycemia. Treatment of hypoglycemia depends on its etiology. Surgical removal of a solitary insulinoma is often curative. However, some causes of hypoglycemia may be difficult to confirm and eliminate, so symptomatic treatment may be the only option.