Several large, randomized, multicenter studies in diabetic and nondiabetic patients with chronic proteinuric nephropathies have clearly demonstrated that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) are able to reduce urinary protein excretion and retard renal disease progression. However, the number of patients who reach end-stage renal failure is still considerable and there is a great need to identify therapies that can arrest evolution of kidney damage. Maximizing renin-angiotensin system (RAS) blockade through combined ACE inhibitor and ARB therapy has been shown to further increase antiproteinuric and nephroprotective effects of each drug class. However, in order to slow to the greatest extent progression of renal disease, the ideal therapeutic approach for patients with proteinuric nephropathies should be a multimodal strategy including dual RAS blockade, antialdosterone therapy, lipid-lowering agents, smoking cessation, and tight glucose control for diabetes.