The renin-angiotensin-aldosterone system (RAAS) plays a dominant role in the pathophysiology of hypertension, diabetes mellitus, chronic kidney disease and chronic heart failure. Therefore, drugs that block key components of the RAAS such as ACE inhibitors (ACEI) and angiotensin receptor blockers (ARBs) have gained wide clinical use for these indications. Despite progress, the morbidity and mortality of patients treated with ACEI or ARBs remain high. Aliskiren (Tekturna, Rasilez) is the first orally active inhibitor of renin approved for clinical use as an antihypertensive agent. The development program has established that at the licensed doses of 150 mg and 300 mg. Aliskiren is effective either as monotherapy or in combination with drugs from the other major classes. In this review we analyze and review the information already gained with Aliskiren, raises questions regarding the advantages of DRIs as monotherapy compared to marketed ACEIs and ARBs, their potential added value in combination with other RAAS modulators and other still unproven benefits in relation to prorenin and renin receptor biology.