See related article, pp 148 -154 P eripheral artery disease (PAD) has been for many years a chapter in cardiovascular diseases that did not attract the interest of clinicians. Intermittent claudication, the most common clinical manifestation of PAD, was considered a rather unimportant symptom. Several new findings published during the last decade have profoundly changed our views on PAD. 1 First, intermittent claudication significantly impacts on the quality of life and on the activities of the patients experiencing it. Moreover, and at least as important, a number of large-scale studies and registries unraveled severely increased risk for coronary and cerebrovascular morbidity and mortality in PAD patients. 2 In fact, this should not surprise us, because the most frequent cause of PAD is, by far, atherosclerosis. The increased risk is of particular importance, because many patients with proven PAD are completely asymptomatic. In such cases, PAD is only detected by clinical examination (absent peripheral pulses) or by measuring ankle brachial pressure index. Whichever way they are detected, the increased risk is present whether the disease is symptomatic or not. Therefore, with all of this in mind, physicians and scientists alike start to realize that PAD should be seen not only as a local problem but also as a marker of atherosclerosis elsewhere in the body.As a consequence, treatment of PAD patients should be oriented at symptoms, if present, but above all, at controlling total CV risk (Table). Symptoms of intermittent claudication are best treated with regular training and smoking cessation; pharmacological approach by drugs like cilostazol or naftidrofuryl can further improve claudication distance. Total risk is controlled by adaptation of lifestyle and antiplatelet therapy. Hypertension often is associated with PAD 3 ; systolic hypertension is especially highly prevalent in PAD patients, most likely because of stiffening of the large arteries. 4 Thus, antihypertensive drugs will be necessary in many PAD patients.There is no convincing evidence of superiority of one antihypertensive drug over another with respect to controlling hypertension in PAD patients or affecting their claudication distance. 5 Slightly better results are obtained by ACE inhibitors, and in some studies an increase in muscle blood flow has been shown; this was accompanied by a limited increase in walking distance (for literature review, see Reference 5 ).There has been a long-standing controversy about using -blocking agents in hypertensive PAD patients. It was postulated that, by blocking the -2-dependent vasodilating effect, the peripheral ␣-1 effect may predominate, leading to vasoconstriction and increase in limb ischemia. However, except in patients with critical limb ischemia, such a negative finding has never convincingly been documented. On the contrary, several studies, including a meta-analysis 6,7 on patients with intermittent claudication, were unable to show a negative effect of -blocking agents in these patients.This que...