Diabetic kidney disease is considered to be an irreversible and inexorable progressive disease. Therefore, prevention of development of ESRD is extremely important. Animal studies have demonstrated that regression of existing renal morphologic lesions is feasible. In a sizable fraction of type 1 diabetic patients with overt nephropathy, remission (decrease in albuminuria to <300 mg/24 h) was obtained (31%), and regression of diabetic nephropathy (rate of decline in GFR < or = 1 mL/min/y), achieved (22%) by aggressive antihypertensive treatment. Furthermore, remission of nephrotic-range albuminuria (from >2500 mg/24 h to <600 mg/24 h) have been demonstrated to be achievable in one fifth of patients with nephrotic-range albuminuria. Remission of nephrotic-range albuminuria was associated with a reduction in decline in GFR and improved survival free of ESRD. However, to prevent development of ESRD in diabetic patients, an aggressive multifactorial approach, aiming at lowering blood pressure and albuminuria, and improving glycemic control, must be applied.