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Increasing attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in the past decade. Compelling data have begun to unite work from various arenas, such as epidemiology and vascular biology. Clinical trials with synthetic PPAR agonists have exhibited therapeutic benefits in treating various chronic diseases like atherosclerosis, diabetes mellitus and cardiovascular diseases. The PPARs, a family of nuclear receptors (NRs), are a set of three receptor sub-types encoded by distinct genes. They function as lipid sensors to regulate a broad range of genes in many metabolically active tissues. The discovery of PPAR-specific ligands has led to a significant advancement in our understanding of the structure of these receptor proteins and molecular mechanisms of their ligand dependent activation. Herein, we have tried to delineate the role of PPARs as molecular targets for the development of new drugs to treat human metabolic diseases.