Background We reviewed the issue of stem cells and therapeutic angiogenesis in the treatment of peripheral vascular disease. Methods MEDLINE (1997–2008) with the following search terms: “stem cell therapy,” “endothelial progenitor cells,” “peripheral blood mononuclear cells,” and “peripheral vascular disease.” Relevant published papers involving the above search terms, preclinical studies, and clinical trials using stem cells and progenitors for the treatment of peripheral occlusive vascular disease were included. Results Transplantation of bone marrow–derived progenitor cells or peripheral blood mononuclear cells promotes tissue angiogenesis, as has already been explored in preclinical studies; angiogenesis can also be sustained using genetic, protein therapeutic approaches. Engineered scaffolding with stem cells is a further strategy, which is still in its infancy. The treatment of patients with severe peripheral arterial disease is generally reported as a series of case reports; all studies generally show an improvement in clinical symptoms, e.g., rest pain and pain-free walking time, as well as transcutaneous oxygen pressure, without any important adverse reactions. The few clinical trials also report similar encouraging results. All the studies have their shortcomings, including absence of control groups and objective evaluation of the results of treatments as well as short-term follow-up. Conclusion Promoting angiogenesis using genetic, protein, stem cell–based therapies is a promising option for the treatment of peripheral vascular disease when unresponsive to medical and surgical therapy.