Most healthcare providers recognize that management of lower extremity wounds presents a difficult challenge. These chronic wounds significantly impact the quality of life for individuals and have implications for costs and utilization of healthcare resources. Lower extremity wounds can be due to a myriad of different diseases, but the primary causes are chronic venous insufficiency, lower extremity arterial disease, and diabetes/neuropathy. Differential assessment is necessary prior to implementation of management strategies in order to address the etiology and pathogenesis factors that are related to each type of leg wound. This article presents an overview of the risk and predisposing factors for venous, arterial, and diabetic/neuropathic wounds. Additionally, it addresses issues of differential assessment including typical locations, common clinical characteristics, typical wound appearance, key management issues, considerations for alternative treatments, collaborative care, and patient/family education.