In parallel with the diabetes pandemic, diabetic kidney disease has become the leading cause of end-stage renal disease worldwide, and is associated with high cardiovascular morbidity and mortality. The early detection and effective management of diabetic nephropathy would delay or prevent the progression of chronic kidney disease. Although the presence of urinary albumin is recognized as an early marker of diabetic nephropathy, significant glomerular damage has already occurred by the time microalbuminuria is present and albuminuria does not necessarily represent the progressive deterioration of renal dysfunction in all, because nephropathy sometimes occurs in the patients without albuminuria. Therefore, more sensitive and specific markers in addition to albuminuria are needed to understand the development and progression of nephropathy in diabetic patients. Although glomerular dysfunction is thought to be a major factor for the development and progression of diabetic nephropathy, tubule-interstitial damage might also play an important role in the pathogenesis of diabetic nephropathy. It has been suggested that an early increase in urinary albumin excretion is relevant to proximal tubular damage or dysfunction in addition to glomerular permeability. These issues in clinical practice have been underestimated because of the limitations of sensitive tests for proximal tubular damage in humans. Therefore, recent studies have focused on several different tubular damage markers clinically indicated as potential biomarkers for the diagnosis of diabetic nephropathy. Identifying biomarkers that can predict diabetic nephropathy in the early stage of diabetes might provide not only meaningful information regarding early pathophysiology but also an earlier clinical approach to the diagnosis and treatment of diabetic nephropathy.