Peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in both developmental and metabolic functions. There are activated by fatty acids, fatty acid metabolites, and synthetic compounds marketed for their lipid-lowering and antidiabetic actions. It was clearly established that activation of PPAR alpha and PPAR gamma, by fibrates and thiazolidinediones, respectively, impair metabolic disorders. The implication of the third member of the PPAR family, PPAR delta, remained evasive until recently. These past few years, it has been demonstrated that treatment with PPAR delta agonists normalizes blood lipids, reduces insulin resistance and adiposity in rodent and primate. Utilization of both cellular and animal models revealed that the nuclear receptor plays a central role in the control of fatty acid burning in adipose tissue and skeletal muscle. Furthermore, PPAR delta appeared to be important for adaptive response of skeletal muscle to environmental changes, such as physical exercise.