Peripheral arterial occlusive disease (PAOD) is now recognized as a combination of clinical syndromes that are associated with significant morbidity and mortality. The primary pathophysiology of PAOD is impaired perfusion to the lower extremity. Effective pharmacotherapy designed to increase perfusion in PAOD is lacking, and revascularization options are suboptimal. New and more efficacious therapies that improve blood flow are definitely needed, and thus designing, describing, and validating these new therapies in preclinical PAOD models will be essential. This study describes the various preclinical PAOD models presently in use, correlates the models to human PAOD, and reviews the available end points that can be used to detect a response to therapy.