The treatment of peripheral artery disease (PAD) focuses on risk factor modification, cardiovascular event reduction, limb viability, and symptom improvement. Hypertension, hyperlipidemia, and diabetes mellitus should all be controlled to recommended target levels, and smoking cessation is vital. Antiplatelet therapies, such as aspirin or clopidogrel, should be administered in all patients unless contraindicated. Whenever possible, patients who present with claudication should be offered a regimen comprised of both medical and exercise therapy, which often results in substantial improvement in symptoms. For patients presenting with more-advanced disease, such as acute limb ischemia, critical limb ischemia, and severely-limiting symptoms of PAD, revascularization is often necessary. As a result of the rapid evolution in endovascular revascularization technology and expertise, many patients with PAD can be treated percutaneously. Therefore, in this Review, we will focus on medical therapy and endovascular revascularization of patients with PAD, with reference to surgical bypass in specific clinical scenarios.