Diabetic nephropathy, by far, is the most common cause of end stage renal disease in the US and many other countries. In type 1 diabetes, the natural history of diabetic nephropathy is tightly linked to evolution of classic lesions of the disease, namely glomerular basement membrane thickening, increased mesangial matrix, and reduced glomerular filtration surface density. These lesions progress in parallel and correlate with increased albumin excretion rate and reduced glomerular filtration rate across a wide range of renal function. In fact, the vast majority of the variances of albumin excretion and glomerular filtration rates can be explained by these glomerular lesions alone in type 1 diabetic patients. Although, classic lesions of diabetic nephropathy, indistinguishable from those of type 1 diabetes, also occur in type 2 diabetes, renal lesions are more heterogeneous in type 2 diabetic patients with some patients developing more advanced vascular or chronic tubulointerstitial lesions than diabetic glomerulopathy. More research biopsy longitudinal studies, especially in type 2 diabetic patients, are needed to better understand various pathways of renal injury in diabetic nephropathy.