Large-scale epidemiologic studies and clinical trials have contributed to an increased recognition of the importance of systolic hypertension. Data from landmark epidemiologic studies such as the Multiple Risk Factor Intervention Trial screenee follow-up and the Framingham Heart Study have demonstrated that elevated systolic blood pressure dramatically increases the risk of cardiovascular events. Of particular concern is the extremely high risk associated with isolated systolic hypertension (ISH), which is much more common in the elderly than in young adults. Clinical trials have identified significant risk reductions after treatment with diuretics or the dihydropyridine calcium antagonist nitrendipine in older individuals with ISH. Beta blockers have not been associated with such benefits. The recently released sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) recommends drug therapy for all patients with stage 1 (140 to 159 mm Hg) or stage 2-3 (> or = 160 mm Hg) systolic hypertension, whether it occurs in isolation or in conjunction with diastolic hypertension. The sixth JNC report identified diuretics as the initial therapy of choice, with a long-acting dihydropyridine calcium channel blocker as an alternative if diuretics are ineffective or not well tolerated. More research is needed to evaluate other classes of drugs in this setting. Regardless of the choice of therapy, patients should be encouraged to adopt lifestyle modifications such as weight loss, exercise, sodium restriction, and reduced alcohol consumption.