In diabetic and nondiabetic chronic nephropathies, high blood pressure and urinary loss of proteins represent major determinants of progressive renal function decline. Reducing blood pressure with drugs that inhibit the renin-angiotensin system also lowers glomerular hypertension and ameliorates glomerular sieving properties, thus reducing proteinuria. Reducing urinary protein levels with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARA) limits renal function decline to the point that remission of disease and regression of renal lesions have been observed in experimental animals and in humans. This therapy, however, may not be effective in all patients. For patients who do not achieve complete remission of proteinuria, renoprotective treatment should include intensified blood pressure control (and metabolic control in diabetes) and amelioration of dyslipidemia. Early intervention, before progressive glomerulosclerosis and scarring is initiated by increased protein traffic, may be important to maximize reno- and cardioprotection, especially in diabetes.