Iatrogenic hypoglycemia is the limiting factor in the glycemic management of diabetes and a barrier to true glycemic control and becomes a progressively frequent clinical problem in advanced type 2 diabetes mellitus. As patients approach the insulin-deficient end of the spectrum of type 2, hypoglycemia results from the interplay of therapeutic insulin excess and compromised physiologic and behavioral defenses against falling plasma glucose concentrations. By practicing hypoglycemia risk reduction, applying the principles of aggressive glycemic therapy, and considering conventional risk factors and those indicative of compromised glucose counterregulation,it is possible to minimize the risk of hypoglycemia and improve glycemic control. Nonetheless, people with diabetes need better treatment regimens.