Chronic lower extremity ulcers are a physical and financial burden to the health and economic establishments worldwide. Foot complications account for about 25% of all diabetic admissions, with 50,000 lower-limb amputations performed annually. Lower extremity wounds are caused by venous disease, arterial insufficiency, diabetic neuropathy, or a combination of these factors. Other etiologies may include vasculitis, TAO/burns, and trauma. The last decade has witnessed a dramatic increase in the mechanistic understanding of angiogenesis and arteriogenesis, the two processes by which the body responds to the obstruction of large conduit arteries. This knowledge has been translated into novel therapeutic approaches to the treatment of peripheral arterial disease. In chronic wounds, senescent cells, due to inhibition of fibroblast proliferation, are unable to divide and hence become unresponsive to growth factors. Stanley and Osler showed that a human venous leg ulcer with more than 15% of senescent cells would be more difficult to heal.Given the poor prognosis associated with critical limb ischemia (CLI), numerous interventions have been attempted, primarily based on the stimulation of angiogenesis to allow the formation of collateral blood vessels. According to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASCII), treatment for CLI should focus on revascularization using surgical or percutaneous means. Unfortunately, less than half of the patients are eligible for these procedures, and efficacy is limited. Additionally, many patients require resurgical interventional procedures due to high levels of restenosis caused by the complex anatomy of the vascular occlusion and/or the presence of other risk factors. Nonsurgical options for CLI are limited to medical therapy, which offers limited or no benefit. Noninvasive stem cell therapy has been proposed as an alternative for such patients. Recent articles on this disease have proposed stem cell therapy along with endovascular procedures as well.