Intermittent claudication is the earliest and the most common presenting symptom of atherosclerotic lower extremity peripheral arterial disease, with a prevalence of 3% to 6% in men aged 60 years. Although claudication may impair community-based walking ability and quality of life in many patients, the fate of claudicant patients is rather benign with respect to their legs, with only 2% of patients needing a major amputation over 5 years. However, patients presenting with claudication are at high risk for cardiovascular events, such as myocardial infarction, stroke and cardiovascular death as a result of coexistent coronary artery and cerebrovascular atherosclerosis. Therefore, appropriate therapeutic goals for claudication include prevention of cardiovascular events and leg disease progression as well as improvement in walking capacity, functional status and quality of life. Until recently, therapeutic recommendations for the prevention of ischemic events in claudicant patients, including long-term antiplatelet therapy and aggressive risk factor modification, have mostly been based on extrapolation from results of studies of patients with coronary heart disease. In the last few years, however, direct, reliable evidence has emerged that supports the use of statins (simvastatin), antiplatelet drugs (aspirin or clopidogrel) as well as angiotensin-converting enzyme inhibitors (ramipril) as secondary preventive treatments in claudication patients. Supervised exercise training is the most effective medical treatment for symptomatic relief in persons with claudication. Several drugs, including pentoxifylline, naftidrofuryl, buflomedil, prostaglandin E1 and the novel agents cilostazol and propionyl-L-carnitine, have also been shown to be effective in improving claudication-related walking impairment, although the benefits appear to be of small magnitude. Drug therapy may have a role in alleviating claudication symptoms when exercise is impossible or ineffective. Alternatively, drugs for claudication may be used to potentiate the benefits of exercise. Promising new pharmacological agents for claudication, including oral prostaglandins, L-arginine, and angiogenic growth factors, are currently being evaluated.