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The three peroxisome proliferator-activated receptors (PPARs), PPARα, δ and γ, form a subfamily of the nuclear hormone receptor gene family. PPARα has been shown to bind and be activated by leukotriene B4 and fibrates, whereas prostaglandin J2 derivatives and the antidiabetic thiazolidinediones, respectively, are natural and synthetic ligands for PPARγ. The availability of ligands and activators for PPARα and PPARγ allowed an initial assessment of their respective functions. PPARα and PPARγ are shown to function as important regulators in lipid and glucose metabolism, adipocyte differentiation, inflammatory response and energy homeostasis. PPARα seems to mediate its pleiotropic effects mainly through the stimulation of oxidation of lipids, whereas PPARγ is a key mediator of lipid storage. The next few years will be very exciting as additional studies will refine our current knowledge about PPARα and PPARγ and may reveal a ligand and role for the lonesome orphan among the PPARs, PPARδ.