BACKGROUND Pharmacologic options for the treatment of elderly patients with type 2 diabetes mellitus (T2DM) are the same as in younger adults; however, treatment considerations differ in the elderly due to changes in renal and hepatic function, life expectancy, and various other clinical and practical considerations. OBJECTIVE This article discusses geriatric considerations in the pharmacologic management of T2DM and reviews the potential clinical advantages and disadvantages of pharmacologic agents currently available for the treatment of T2DM, including oral and injectable medications. METHODS A search of MEDLINE was conducted for articles published in English between January 1966 and September 2009 using the terms type 2 diabetes mellitus, elderly, geriatric, treatment, insulin, metformin, sulfonylurea, thiazolidinedione, alpha-glucosidase inhibitor, meglitinide, DPP-4 inhibitor, colesevelam, exenatide, and pramlintide. Meta-analyses, randomized controlled trials of pharmacologic treatment, and evidence-based reviews and/or expert opinions regarding the treatment of T2DM in the elderly were selected for review. RESULTS In overweight patients, metformin has been associated with reductions in risk for all-cause mortality and stroke compared with insulin and sulfonylureas. Older patients who are frail, anorexic, or underweight and those with congestive heart failure (CHF), renal or hepatic insufficiency, or dehydration may not be appropriate candidates for metformin therapy. The substantial risk of hypoglycemia with insulin secretagogues is increased by 36% in the elderly compared with younger adults; however, this risk is counterbalanced by the extensive clinical experience with these agents in the geriatric population. Thiazolidinediones should generally be avoided in patients with CHF and are absolutely contraindicated in patients with class II-IV heart failure. They have been associated with peripheral edema, as well as with decreases in bone mineral density in women. There is limited information on the use of dipeptidyl peptidase-4 inhibitors in the elderly, although dose adjustment is required in patients with renal compromise. In practice, substantial gastrointestinal adverse effects limit the use of alpha-glucosidase inhibitors in older patients. Colesevelam is associated with numerous drug interactions and can cause new or worsening constipation. There are limited data on the use of exenatide in the elderly. It may be beneficial in older patients with limited mobility who could benefit from weight loss, whereas it may not be a good option for frail, underweight adults. Use of exenatide is not recommended in patients with a creatinine clearance <30 mL/min. Given the increased monitoring required to avoid hypoglycemic events with pramlintide, this agent should be used with caution in older adults, particularly the frail elderly. Most patients with T2DM eventually require insulin; however, due to the risk of hypoglycemia and related morbidity, careful use of insulin is warranted in the geriatric population. CONCLUSIONS Overall, there is a scarcity of data regarding the use of pharmacologic agents in older adults with T2DM, and clinical guidance is largely based on data obtained from younger populations. The selection of appropriate drug regimens for these patients remains challenging.