Modification of the renin-angiotensin-aldosterone system by renin inhibitors may be an alternative to angiotensin-converting enzyme inhibitors in the treatment of cardiovascular disease. The development of clinically useful renin inhibitors has been hampered by a variety of pharmacologic problems, most notably the poor oral bioavailability of these peptide-related compounds. Peptidomimetic renin inhibitors that have been stabilized to enzymatic degradation in conjunction with optimizing physical characteristics amenable to intestinal absorption offer the greatest promise to date. Studies in animal models demonstrate that renin inhibitors are capable of reducing both systolic and diastolic blood pressures without causing reflex tachycardia. The response appears to be sustained with chronic administration. The beneficial cardiovascular effects of these compounds have been confirmed in the few studies conducted in patients with hypertension and in those with congestive heart failure. Further development of renin inhibitors is warranted.