The prevalence of peripheral artery disease is steadily increasing and is associated with significant morbidity, including a significant percentage of amputations. Peripheral artery disease often goes undiagnosed, making its prevention increasingly important. Patients with peripheral arterial disease are at increased risk of adverse cardiovascular outcomes which makes prevention even more important. Several risk factors have been identified in the pathophysiology of peripheral artery disease which should be modified to decrease risk. Smoking, hyperlipidemia, hypertension, and diabetes are among proven risk factors for the development of peripheral artery disease, thus smoking cessation, lipid control, blood pressure control, and glucose control have been tried and shown to be effective in preventing the morbidity associated with this disease. Pharmacologic agents such as aspirin and clopidogrel alone or in combination have been shown to be effective, though risk of bleeding might be increased with the combination. Anticoagulation use is recommended only for acute embolic cases. Other treatment modalities that have been tried or are under investigation are estrogen replacement, naftidrofuryl, pentoxifylline, hyperbaric oxygen, therapeutic angiogenesis, and advanced glycation inhibitors. The treatment for concomitant vascular diseases does not change in the presence of peripheral artery disease, but aggressive management of risk factors should be undertaken in such cases.