Inhibitors of the RAAS are safe and effective in lowering blood pressure. Two prospective studies (Captopril Prevention Project [CAPPP] and the Swedish Trial in Old Patients-2 With Hypertension [STOP-Hypertension II]) showed that this class of drugs reduced morbidity and mortality in patients with hypertension similar to conventional therapy (diuretics and β- blockers). In the Heart Outcome Prevention Evaluation (HOPE) study, an impressive reduction of morbidity and mortality was achieved by ramipril in a heterogeneous group of patients with cardiovascular risk factors. Use of ACE inhibitors as first-line therapy in hypertension and CHF therefore seems justified. However, ARBs are better tolerated than ACE inhibitors and therefore may become a preferred alternative to ACE inhibitors, although ACE inhibitors cost less. Angiotensin II receptor blockers should be substituted for ACE inhibitors when class-specific adverse effects occur. The fact that clinical effects and adverse effects are not identical and the combination of 2 drug classes increases efficacy in some patients makes it unlikely that ARBs will ever be complete substitutes for ACE inhibitors. Results from ongoing prospective studies are needed to answer some of these questions.