Among many challenges to achieving and maintaining glycemic control, the impact of pharmacologic agents on glycemia is a significant, but often overlooked factor. Numerous medications have been implicated in the development of drug-induced hyperglycemia and type 2 diabetes mellitus. Of these, the atypical antipsychotics (for the management of depression and psychosis), the protease-inhibitor anti retroviral agents (for the management of HIV and AIDS), immunosuppressive medications, niacin, and certain antihypertensive agents are the most prevalent. Caffeine is another prevalent, although nonprescription, drug with important metabolic effects. An understanding of the potential effects of these drugs on glucose metabolism is important for the care of patients with type 2 diabetes and for those at risk for the development of diabetes.