Atherosclerosis remains a major complication of type 2 diabetes mellitus. Increasing data suggest insulin resistance, and its associated metabolic abnormalities, may underlie many of the cardiovascular complications seen among patients with insulin resistance and/or diabetes mellitus. This insight has also suggested that therapeutic approaches targeting insulin resistance may not only improve metabolism but also limit complications like atherosclerosis and the inflammation that contributes to it. Thiazolidinediones, agonists of the nuclear receptor peroxisome proliferator activated receptor gamma, are one such insulin-sensitizing therapeutic intervention in current use among patients with type 2 diabetes mellitus. The existing data regarding thiazolidinedione effects on the cardiovascular system are reviewed and considered, along with the future prospects for this emerging drug class.