Hypoglycemia is uncommon in the general, nondiabetic population but occurs frequently in persons with diabetes treated with insulin or insulin secretagogues. Thus, iatrogenic hypoglycemia explains the majority of cases among persons with type 1 diabetes (T1DM). Since T1DM is characterized by absolute insulin dependence, the current imperfections in insulin replacement therapies often lead to a mismatch between caloric supply and circulating insulin levels, thus increasing the risk for glycemic fluctuations. Hypoglycemia is the limiting factor to excellent glycemic control in insulin-treated subjects. Intensification of glycemic control was associated with a 300 % increase in the rate of hypoglycemia in the Diabetes Control and Complications Trial. Recent measurements using continuous glucose monitoring reveal an alarming rate of daytime and nocturnal episodes of hypoglycemia in patients with T1DM. Etiological factors underlying hypoglycemia in T1DM include predictable triggers (skipped meals, exercise, insulin over dosage) as well as defective counterregulation, a component of hypoglycemia-associated autonomic failure.