Peripheral artery disease (PAD) is a marker of systemic atherosclerosis. Most patients with PAD also have concomitant coronary artery disease (CAD), and a large burden of morbidity and mortality in patients with PAD is related to myocardial infarction, ischemic stroke, and cardiovascular death. PAD patients without clinical evidence of CAD have the same relative risk of death from cardiac or cerebrovascular causes as those diagnosed with prior CAD, consistent with the systemic nature of the disease. The same risk factors that contribute to CAD and cerebrovascular disease also lead to the development of PAD. Because of the high prevalence of asymptomatic disease and because only a small percentage of PAD patients present with classic claudication, PAD is frequently underdiagnosed and thus undertreated. Health care providers may have difficulty differentiating PAD from other diseases affecting the limb, such as arthritis, spinal stenosis or venous disease. In Part 1 of this Review, we explain the epidemiology of and risk factors for PAD, and discuss the clinical presentation and diagnostic evaluation of patients with this condition.