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To review the clinical benefits of inhibiting the renin–angiotensin system (RAS) through blood pressure (BP)–lowering and BP-independent mechanisms and to identify the benefits and potential limitations of RAS-blocking agents in various patient populations.PubMed search using the key terms renin-angiotensin system, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aliskiren, heart failure, diabetes, and nephropathy. Current published guidelines from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, American Diabetes Association, and National Kidney Foundation were reviewed.Antihypertensive treatment with an agent that inhibits the RAS effectively lowers BP in a broad range of patients. Whether these agents improve clinical outcomes is the subject of ongoing investigation. Results of recent trials suggest that for patients with or at risk of high-risk conditions, such as heart failure or diabetes, risk reduction with RAS-blocking agents may be independent of BP reduction. Inhibition of the RAS may also reduce risk of renal impairment.RAS-blocking agents are important in a variety of patient populations at high cardiovascular risk, but while angiotensin-converting enzyme inhibitors have proven benefits in some cases, angiotensin receptor blockers may be preferred in others. Direct renin inhibitors are currently being evaluated. The nurse practitioner should become familiar with the evidence for use of these agents to reduce risk and improve outcomes in specific populations.