The association between hyperlipidemia and renal disease was noted by Virchow as early as the 19th century. Subsequently, similar histopathological lipid depositions were confirmed-in diverse human and experimental renal disease. Although, no studies have been established in man to suggest a causal relationship between lipids and the pathogenesis of renal disease, compelling evidence accumulated in experimental animals suggests a direct role of lipids in the initiation and progression of glomerular disease. These studies showed that cholesterol-feeding to various experimental animals induced the development of glomerular injury. Furthermore, the treatment of hyperlipidemic animals with lipid lowering drugs prevented the development of glomerulosclerosis. In this article, we will review recent advances made in understanding various aspects of lipid-mediated renal injury including biochemical mechanisms of hyperlipidemia, a possible direct role of hyperlipidemia in the pathogenesis of renal disease, pathobiological accumulation of lipids and lipoproteins, biochemical and histological similarities between systemic atherosclerosis and glomerulosclerosis, and cellular processes involved in the development of glomerular disease. Furthermore, we will define cellular and molecular hypotheses that provide putative mechanisms by which hyperlipidemia and atherogenic lipoproteins induce series of cytoregulatory peptide-mediated events involved in the development of glomerular disease.