Claudication is the most common symptom indicating arterial insufficiency of the lower extremities. The most common cause of claudication is atherosclerosis. However, when claudication occurs in a younger individual in whom the suspicion of atherosclerosis is low, other causes of exercise-induced leg discomfort should be considered. Some of these disorders are: Thromboembolism, thromboangiitis obliterans, popliteal artery entrapment syndrome (PAES), cystic adventitial disease, fibromuscular dysplasia, ergotamine ingestion, popliteal artery aneurysm, vasculitis, and connective tissue diseases. This chapter precludes discussion of all of these disorders; therefore, only the more common and important causes are discussed. Other less common types of vascular disease are also described. Most commonly, a healthy, “athletic-type” male notes typical claudication symptoms in the absence of evidence of premature atherosclerosis. Once the diagnosis of PAES is made, surgical intervention is warranted regardless of symptoms. Surgical repair prevents thrombotic and embolic complications, which can be quite serious.