Pamela KushnerUniversity of California, Irvine College of Medicine, California, USAAbstract: Hypoglycemia is a major barrier to achieving glycemic goals in patients with diabetes. Both acute and chronically recurrent hypoglycemic events appear to have long-term consequences for patients with type 2 diabetes mellitus (T2DM). Chronically recurrent hypoglycemia may lead to an impairment of the counterregulatory system, with the potential for the development of hypoglycemia unawareness syndrome, increased severe hypoglycemia-associated hospitalization, and increased mortality. Hypoglycemic events may also have negative implications in cardiovascular disease and/or dementia. Avoidance of hypoglycemia by treating with appropriate, individualized regimens for patients with T2DM should be a primary focus of physicians. Utilizing traditional agents (eg, metformin and thiazolidinediones) that do not promote hypoglycemia, in combination with newer agents such as dipeptidyl peptidase-4 inhibitors and incretin mimetics, could offer a therapeutic advantage when trying to help patients reach their hemoglobin A1c goal without the added risk of hypoglycemia.Keywords: hypoglycemia, type 2 diabetes mellitus, incretin, dipeptidyl peptidase-4 inhibitors, diabetes management