The arterial occlusive diseases of the lower extremities represent a spectrum of disorders encompassing myriad etiologies. The normal “end-organ” functions of the lower and upper extremities are (1) to permit independent ambulation, and (2) to manipulate objects; thus, diseases that alter normal limb function may potentially elicit major disabilities. Although the most common cause of lower extremity arterial occlusive disease in Western societies remains atherosclerosis, other disorders may perturb normal limb perfusion. The extremity arteries are susceptible to congenital, inflammatory, and degenerative diseases, including fibromuscular dysplasia, thromboangiitis obliterans (Buerger’s disease), vascular entrapment syndromes, and both arterial thromboembolism and atheroembolism. The consideration of a broad differential diagnosis is essential for establishing an effective diagnostic and individualized treatment plan.