Isolated systolic hypertension is the most common type of hypertension in the elderly. A number of trials have widely shown that it is an independent risk factor for cardiovascular morbidity and mortality. This review focuses the prevalence of isolated systolic hypertension, its pathophysiology, diagnosis and treatment. The optimal treatment strategy is to maximize reduction in systolic blood pressure and to minimize reduction in diastolic blood pressure. All classes of antihypertensive agents can be used, but calcium antagonists, ACE-inhibitors and, more recently, the angiotensin II antagonists appear to be more successful in improving large artery stiffness and therefore are especially useful in treating isolated systolic hypertension in the elderly. A careful evaluation and treatment has to be made in particular in those patients with more risk factors, in order to choose the most appropriate drug and to avoid dangerous drug-drug interactions where polypharmacy occurs.