The thiazolidinediones (TZDs) are agonists for peroxisome proliferator-activated receptor-γ (PPARγ), and they promote insulin sensitization and improve dyslipidemia in patients with type 2 diabetes mellitus. PPARγ is widely expressed, both in circulating and renal parenchymal cells. The TZDs are widely used clinically to improve metabolic syndrome, but may also have beneficial effects on progressive renal damage beyond diabetes. PPARγ agonists also have direct benefits on progressive renal injury independent of altering the metabolic profile, including effects on inflammation and oxidative stress.Wewill reviewselected evidence of such actions of PPARγ agonists beyond metabolism and examine interactions with other key pro-fibrotic mediators, including transforming growth factor-β (TGF-β) and the renin-angiotensin system (RAS).