Hypertension has a worldwide high incidence in the general population and undoubtedly it is the most important risk factor for cardiovascular morbidity and mortality, in industrialized countries. In this Review we investigated the role of angiotensin II receptor antagonists (ARBs) therapy in the treatment of essential hypertension. We selected in the PubMed and in a list of selected sources the most significant clinical trials and meta-analysis carried out from 1999 to now, to assess, in adult patients populations, ARBs' efficacy, safety and tolerability profile, in comparison with the efficacy of the other common antihypertensive drugs, with particular regard to both the prevention of disabling consequences of hypertension (like cerebrovascular events, coronary events and heart failure) and the influence of an adequate antihypertensive therapy on comorbidities which strongly influence the outcome of hypertensive patients (like atherosclerosis, kidney damage, type II diabetes mellitus and arrhythmias). We also evaluated, in a detailed pharmacological and pharmaco-economic analysis, the basilar differences between ACE-inhibitors and ARBs in the control of the RAA system, and we assessed the possible benefits of their associated use, according to the new evidences concerning the treatment of arterial hypertension.