Dual blockade of the renin-angiotensin system (RAS) with a combination of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the treatment of hypertension and proteinuria has been tested in several randomized trials among patients with chronic kidney disease (CKD). Although combination therapy reduces proteinuria and blood pressure, adequately powered studies evaluating time to end-stage renal disease, death, or cardiovascular outcomes in patients with CKD have not been done. Dual blockade of RAS can cause hyperkalemia, renal failure, and orthostatic hypotension and potentially worsen outcomes; therefore, the risk-benefit ratio in patients with CKD remains unclear. A recent randomized trial in patients with cardiovascular disease or high-risk diabetes raises concerns about the safety of this combination therapy.