Dipeptidyl peptidase-4 (DPP-4) inhibitors are some of the newest medications in our armamentarium for the management of type 2 diabetes mellitus. Through inhibition of the DPP-4 enzyme, these agents increase the amount of circulating incretin hormones, leading to an increase in insulin release and a suppression of glucagon secretion. Linagliptin is the third DPP-4 inhibitor approved by the Food and Drug Administration in the United States. It has been studied as monotherapy and as an adjunctive therapy to other oral agents in a dual or triple combination regimen. Linagliptin lowers glycosylated hemoglobin by about 0.4% when used as monotherapy and by about 0.5% to 1.1% when used in combination with other oral antihyperglycemic agents. Since linagliptin is mostly eliminated via the enterohepatic system (80%) and not to a significant extent through renal excretion, dosage adjustment is not necessary in patients with renal impairment. Linagliptin also has a favorable safety profile; nasopharyngitis is one of the more common observed side effects. Given its encouraging safety and efficacy profile, linagliptin is a good alternative to the other 2 agents in this class, especially for patients with renal impairment. This article provides a review of the pharmacologic and pharmacokinetic properties of linagliptin. The differences among the 3 available DPP-4 inhibitors will also be examined.