The choice of antihyperglycemic agents has become more complex as new drug classes have appeared and evidence about their efficacy and safety accumulates. Unfortunately, direct and fair comparisons are lacking and the clinician and patient are left to decide among agents with different safety and burden profiles. Furthermore, the relative efficacy of these agents beyond their ability to lower hemoglobin A1c - that is, in their ability to reduce the risk of diabetes complications - remains uncertain. In this sea of uncertainty, interests other than those of the patient actively shape choices. It is our expectation that better evidence, better policy and better decisions will eventually become routine in the care of patients with diabetes.