Isolated systolic hypertension (ISH) has proved to be a powerful predisposing factor for cardiovascular diseases in the elderly. Recent placebo-controlled interventional trials such as the Systolic Hypertension in the Elderly Program (SHEP), the Systolic Hypertension in Europe (Syst-Eur), and the Systolic Hypertension in China (Syst-China) showed that the lowering of systolic blood pressure using a diuretic- or a calcium antagonist-based treatment is associated with a decrease in cardiovascular events. Antihypertensive therapy was found especially effective in preventing stroke in the elderly with ISH. A slowing in the progression of dementia was observed in patients randomized to a calcium antagonist-based treatment. Patients at high cardiovascular risk such as those with diabetes benefited the most from treatment. In another trial performed in patients with left ventricular hypertrophy (Losartan Intervention For Endpoint Reduction ), a subset of patients had ISH. In those patients, an angiotensin II antagonist-based treatment was superior to a b-blocker-based treatment in preventing cardiovascular complications. The experience accumulated in patients with ISH showed that combination therapy is often required to control blood pressure. Overall, the evidence available today indicates that pharmacologic treatment of ISH markedly improves the outcome of elderly patients.