Apolipoprotein E (ApoE) is a major constituent of plasma lipoproteins with many biological actions of great significance. Beyond the known influence of ApoE polymorphisms on serum lipid profile, the pathogenesis of atherosclerosis, and the development of neurodegenerative disorders, ApoE also has a major role in the pathogenesis and progression of a variety of renal diseases, as well as in the atherosclerotic complications associated with them. Briefly, the polymorphisms of ApoE are major determinants of plasma lipid levels in uremic patients. They may affect the risk for cardiovascular disease in this population, predispose to the development of diabetic nephropathy, influence the severity of certain glomerulopathies, and regulate mesangial and glomerular functions locally in the kidney microenvironment. Finally, certain mutations of the ApoE gene are associated with a recently described nephropathy, termed lipoprotein glomerulopathy.