Hypoglycemia is an important complication of glucose-lowering therapy in patients with diabetes mellitus. Attempts made at intensive glycemic control invariably increases the risk of hypoglycemia. A six-fold increase in deaths due to diabetes has been attributed to patients experiencing severe hypoglycemia in comparison to those not experiencing severe hypoglycemia Repeated episodes of hypoglycemia can lead to impairment of the counter-regulatory system with the potential for development of hypoglycemia unawareness. The short- and long-term complications of diabetes related hypoglycemia include precipitation of acute cerebrovascular disease, myocardial infarction, neurocognitive dysfunction, retinal cell death and loss of vision in addition to health-related quality of life issues pertaining to sleep, driving, employment, recreational activities involving exercise and travel. There is an urgent need to examine the clinical spectrum and burden of hypoglycemia so that adequate control measures can be implemented against this neglected life-threatening complication. Early recognition of hypoglycemia risk factors, self-monitoring of blood glucose, selection of appropriate treatment regimens with minimal or no risk of hypoglycemia and appropriate educational programs for healthcare professionals and patients with diabetes are the major ways forward to maintain good glycemic control, minimize the risk of hypoglycemia and thereby prevent long-term complications.