Diabetic nephropathy is the most common cause of end stage renal failure (ESRF) in the developedof world and as the incidence of diabetes increases this trend will continue, although most of these patients will die of cardiovascular diseases. The renin-angiotensin system (RAS) is believed to play a central role in the development and progression of both micro- and macrovascular complications of diabetes and blocking this system in diabetic patients is critically important. Two widely used inhibitors of RAS are angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). These drugs affect the system at different levels and thus may have an additive effect. Use of drugs from one class may not be completely effective in blocking this system for several reasons. In this article we discuss issues surrounding the use of dual blockade (i.e. the use of ARB and ACE inhibitors together in patients with diabetic nephropathy responding insufficiently to previous antihypertensive treatment including either ARB or ACE inhibitors) in patients with diabet