Peripheral arterial disease (PAD) includes a wide range of manifestations in the lower limb, from asymptomatic to symptomatic disease ranging from intermittent claudication to critical limb ischemia, with ulcers, rest pain, or gangrene. It is manifestation of generalized atherosclerosis and this is clearly shown by the high prevalence of coexistence coronary and cerebral arterial disease in these patients. The cumulative findings on molecular and cellular biology have dramatically changed our concept of atherosclerotic disease. Recently, it has become clear that inflammation is fundamental to the process of atherosclerosis. Although the relation between inflammation and PAD is not well characterized, the emerging data demonstrated that PAD is a common manifestation of atherosclerosis that is associated with a systemic inflammation. The most important risk factors for PAD are similar to those of atherosclerotic disease elsewhere: age, male sex, diabetes mellitus, smoking, hypertension, hyperlipidemia, and hereditary factors. Serum levels of inflammatory markers, especially after exercise, have been found to be higher in patients with PAD than in controls, and associated with prognosis as well as restenosis in patients with PAD after revascularization. In the general United States adult population, inflammation is independently associated with PAD in a cross-sectional, nationally large representative sample. All of those evidences indicate that PAD is one aspect of atherosclerosis, a disease rationally connects with inflammation, which may further change our preventive and therapeutic strategies.