Patients with peripheral artery disease and generalized atherosclerosis are at high risk of cardiovascular and limb complications, affecting both quality of life and longevity. Lower limb atherosclerotic disease is associated with high cardiovascular morbidity and mortality and adequate management is founded on treatments involving patient-dependent factors, such as lifestyle changes, and physician-dependent factors, such as clinical treatment, endovascular treatment, or conventional surgery. Medical management of peripheral artery disease is multifaceted, and its most important elements are reduction of cholesterol level, antithrombotic therapy, control of arterial blood pressure, control of diabetes, and smoking cessation. Adhesion to this regime can reduce complications related to the limbs, such as chronic limb-threatening ischemia, that can result in amputation, and the systemic complications of atherosclerosis, such as stroke and myocardial infarction.