Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis that is characterized by obstruction of the arteries in the lower limbs. Experimental and epidemiological studies suggest a key role for oxidative stress in initiation and progression of the atherosclerotic process. The results of these studies provided a good basis for interventional trials with antioxidants, particularly with vitamin E, but the findings were conflicting. In this paper we review the observational and interventional studies with antioxidants, and ask whether vitamin supplementation should be recommended for PAD patients.