Peripheral arterial disease (PAD) is a clinical setting affecting more than 5% of population older than 60. Despite the low rate of peripheral complications and amputation, PAD is complicated by high rate of coronary and cerebral events. For this reason PAD is considered a marker for systemic atherosclerosis and its early diagnosis may be helpful for identifying patients at risk for cardiovascular events. Experimental and epidemiological studies suggest a key role for oxidative stress in initiation and progression of the atherosclerotic process. In several clinical settings of atherosclerotic disease patients have evidence of enhanced oxidative stress but it is unclear if this finding helps to identify those who are at higher risk of cardiovascular complications. More limited are the data concerning the antioxidant status, that is a reflection of oxidative stress and should be lowered in case of diminished defence against oxidative stress. Despite the lack of this data many clinical trials have been done on the assumption that antioxidants could be of benefit in patients with atherosclerosis but the results have been disappointing. Because PAD is characterised by systemic atherosclerosis, it should be considered an interesting model to study the balance between oxidative stress and antioxidant status. This hypothesis is also based on the fact that PAD patients have several risk factors of atherosclerosis that are associated with enhanced oxidative stress. This paper will review the data concerning the balance between oxidative stress and antioxidant status in PAD trying to assess if in this clinical setting a rationale for the use of antioxidants does exist.