Whether symptomatic or not, peripheral arterial disease (PAD), atherosclerosis in the arteries of the lower extremities, is a common disorder in the general population. The prevalence increases with age and under the influence of vascular risk factors. The most classic symptomatic expression of PAD is intermittent claudication. However, the majority of patients with PAD is asymptomatic or has leg symptoms other than classic intermittent claudication. Both symptomatic and asymptomatic subjects with PAD have increased mortality rates, mainly due to cardiovascular and cerebrovascular expressions of atherosclerotic disease. This review focuses on the current available medical therapies for PAD, including risk-factor modification and antiplatelet therapies, as well as strategies for symptomatic relief in both patients with intermittent claudication and patients with critical limb ischemia. In general, risk factor modification and antiplatelet therapy is essential in all patients with PAD to prevent systemic atherosclerotic complications. Furthermore, for symptomatic relief exercise therapy is the main intervention while pharmacological treatment should be only complementary. In patients with critical limb ischemia, when revascularization therapy is not possible, an attempt should be made to avoid amputation with conservative treatment using analgesics, vasodilators and/or anticoagulants. In case of an acute onset of critical limb ischemia, thrombolysis is indicated.