Multisite artery or polyvascular disease is common. In the REACH registry, 15.9% of patients with either established atherosclerotic arterial disease or at least 3 risk factors for atherothrombosis had symptomatic polyvascular disease. History of risk factors and known co-morbidities, as well as a thorough physical examination, are mandatory in the initial screening and diagnostic work-up. Various non-invasive imaging techniques (duplex ultrasound, computed tomography angiography, magnetic resonance angiography) can be used for the identification of the polyvascular patient. Digital subtraction angiography is now used almost exclusively in association with endovascular procedures. Appropriate implementation of each technique is based on international guidelines and a multidisciplinary discussion for each case.The presence of co-existing disease in a different vascular bed is associated with a higher risk of recurrent symptoms and complications in the first site. In this context, accumulating evidence suggests that arterial biomarkers, such as arterial stiffness (pulse wave velocity), central blood pressures, wave reflections indices, ankle-brachial index, carotid intimamedia thickness, as well as vasculogenic erectile dysfunction, can predict cardiovascular morbidity and mortality beyond classical risk factors and prediction models. An important pending question is whether identification of multisite arterial disease may improve clinical outcomes in patients who are already in secondary prevention programs. Such screening of asymptomatic multisite artery disease in patients with known CVD would be of paramount importance if it is ultimately proven with hard evidence that it should lead to a different management from the one proposed for CVD patients without multisite artery disease.