Troglitazone, which was first synthesized in 1983, is a compound with the characterizations of both thiazolidinedione and vitamin E and a physiologic effect to reduce insulin resistance. Because insulin resistance is a major risk factor for the development of type 2 diabetes and a principal impediment to achieving good metabolic control, there is an inherent logic in using a compound with this potential effect. In the United States, troglitazone was approved for clinical use in 1997, with an initial indication as adjunctive therapy for insulin-treated patients with type 2 diabetes, and later this was extended for use as monotherapy and in combination with sulfonylureas in the treatment of type 2 diabetes mellitus. Approximately 800,000 patients in the United States, the United Kingdom, and Japan have been treated with troglitazone since its introduction in early 1997. Accordingly, there is a growing body of literature concerning the clinical efficacy and safety of troglitazone, and a principal focus of this review is to examine these data. Interest in understanding the mechanism of action of troglitazone has also been considerable.