Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) plays a critical role in glucose and lipid metabolism. More recently, PPAR‐γ ligands have been reported to inhibit the expression of proinflammatory molecules by monocytes/macrophages. Of relevance to CNS disease is that PPAR‐γ agonists have been demonstrated to have similar effects on microglia. PPAR‐γ agonists also ameliorate experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. This Mini‐Review summarizes the effects of PPAR‐γ agonists in mediating immune responses and the potential of these agonists in the treatment of inflammatory disorders of the CNS. © 2002 Wiley‐Liss, Inc.