Atherosclerosis represents one of the most relevant causes of death and morbidity worldwide. Peripheral artery disease (PAD), due to the localization of atherosclerosis on lower limb, may lead to disability, amputation, and increased risk of cardiovascular events and death with a significant burden on public health. The clinical manifestation of PAD may significantly vary based on the stage of arterial occlusion and to the patients characteristics, from asymptomatic to seriously disabling. PAD diagnosis may thus be really relevant especially in the first stage, where a prompt intervention might have the best outcome. In this chapter, we will introduce the diagnostic approach to the patient at risk of asymptomatic PAD, and intermittent claudication, discuss the role of PAD in cardiovascular risk and review the most recent evidence on the management of this condition.