Renin inhibitors may offer an exciting new therapeutic means of blocking the action of the renin-angiotensin-aldosterone system. These compounds interfere with the first, rate-limiting step in the synthesis of angiotensin II by binding directly to the highly specific enzyme, renin. This approach may represent a more focused alternative to angiotensin-converting enzyme inhibitor therapy with an improved side-effect profile. Renin inhibitors given parenterally safely lower blood pressure in patients with essential heart failure. Under conditions of salt limitation, normal subjects show increases in renal plasma flow during infusion of renin inhibitors. The systemic and renal hemodynamic responses to renin inhibition are accompanied by suppression of plasma renin activity, plasma angiotensin II and plasma aldosterone levels. Recent scientific advances in discovering how to address the limitations of the low oral bioavailability of peptide-based compounds have made it possible to invent orally active renin inhibitors. Orally active renin inhibitors are presently being evaluated in clinical trials. The availability of intravenous and oral delivery of renin inhibitors broadens the potential of these agents to treat a wide variety of acute and chronic cardiorenal disorders.