Peroxisome proliferator-activated receptors (PPARs) are the key transcription factors regulating lipid metabolism and energy homeostasis. PPARα and PPARγ are known therapeutic targets for hypertriglyceridemia and type 2 diabetes, respectively. The physiologic function of the third member, PPARδ, has been difficult to define due to its broad tissue distribution. Through the creation of transgenic mouse models and identification of high-affinity synthetic ligands, the diverse activities of PPARδ in several metabolically active tissues, including skeletal muscle, adipose tissue, liver, and macrophages, have recently been revealed. These metabolic activities of PPARδ implicate the potential use of PPARδ agonists to treat metabolic diseases, including atherosclerosis and insulin resistance.