KEY POINTS AND PRACTICAL RECOMMENDATIONS: • Aliskiren, the sole oral renin inhibitor approved by the US Food and Drug Administration, is indicated for the treatment of hypertension, either as monotherapy or in combination, with reductions in blood pressure similar to other agents. • Early evidence suggests that aliskiren confers additional benefit in patients with diabetic nephropathy. Data are not yet available to determine whether protection will extend to cardiovascular disease. • No initial dosage adjustment is required in elderly patients or for patients with mild to severe renal impairment; however, clinical experience is limited in patients with significant renal impairment, and with renal artery stenosis. • It appears rational to combine aliskiren with agents that otherwise increase plasma renin activity, including thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. • While there is a reactive rise in renin in response to aliskiren, probably larger than that induced by angiotensin receptor blockers and angiotensin-converting enzyme inhibitors, there is no evidence that this rise is harmful. • In placebo-controlled studies, the incidence of edema anywhere in the body was 0.4% with aliskiren compared with 0.5% with placebo. It is unknown whether angioedema rates are higher in blacks with aliskiren. • Aliskiren is associated with a slight increase in cough, with rates of about one third to one half seen with angiotensin-converting enzyme inhibitors. • Increases in serum potassium >5.5 meq/L were infrequent in patients with essential hypertension treated with aliskiren alone (0.9% compared with 0.6% with placebo).