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Direct Renin Inhibitors (DRIs) are a new class of medication, and are the first which block the rate-limiting step of the renin-angiotensin-aldosterone-system (RAAS). Aliskiren, the first licensed orally active DRI, has been shown to be an effective antihypertensive agent. This review article outlines the pharmacological basis for DRI therapy, from discovery of the class to ongoing clinical trials and novel therapeutic applications of aliskiren.