Approximately two-thirds of the elderly population has hypertension, mainly of the isolated systolic hypertension (ISH) type. However, while large-scale, randomized controlled intervention trials have demonstrated that treatment of ISH reduces rates of total mortality, cardiovascular mortality and stroke in older hypertensives, control of ISH in the elderly remains poor. The aim of this review of drug treatment of ISH in the elderly is to provide a succinct, practical and clinically orientated guide that summarizes international recommendations and practices with special emphasis on newer approaches. Knowledge of pathophysiological changes in older subjects (decreased elastic artery compliance, reduced plasma renin activity, increased salt sensitivity) and evidence from epidemiological surveys and randomized controlled trials give clear clues that thiazide(-like) diuretics and long-acting dihydropyridine calcium channel antagonists are the drugs of choice in the treatment of ISH. Thus, based on this evidence, American, European and international guidelines for hypertension management still offer the best available recommendations for optimal treatment of ISH in the elderly. Newer combination treatments, especially the fixed combination of a dihydropyridine calcium channel antagonist and an ACE inhibitor, have valuable benefits in terms of efficacy and tolerability. Use of nitrates added to other antihypertensive medications can provide the practising physician with a further unconventional therapeutic strategy.