Along with coronary artery disease and cerebrovascular disease, peripheral artery disease (PAD) is primarily caused by atherosclerosis. In fact, PAD is a marker of advanced atherosclerotic disease, as evidenced from several studies that suggest approximately 60% of patients with PAD have polyvascular disease or manifestations of atherosclerosis in the coronary or cerebrovascular territories as well. However, despite a PAD prevalence that is > 15% in patients with cardiovascular risk factors aged 60 to 69 years and > 35% in patients aged 70 to 82 years, there is a lack of disease awareness on the part of both physicians and patients. This lack of awareness most likely contributes to the high cardiovascular risk associated with a diagnosis of PAD. For example, in the Reduction of Atherothrombosis for Continued Health (REACH) Registry, patients with PAD experienced the highest rates of all-cause mortality, cardiovascular death, myocardial infarction, stroke, or hospitalization for atherothrombotic events. High-risk patients should be screened for the presence of PAD. If diagnosed, physicians should institute a comprehensive treatment strategy that includes lifestyle modification and appropriate risk-reducing therapies. Because PAD is a manifestation of atherosclerosis, antiplatelet therapy should be a critical component of any PAD treatment plan. This article reviews the epidemiology and cardiovascular risks associated with PAD, as well as available diagnostic and treatment options.