Objective To review the studies on vascular endothelium growth factor (VEGF) gene therapy for patients with chronic critical limb ischemia. Methods Advance in molecular biology of VEGF, mechanism of new vessel formation induced by VEGF and achievement of improving blood flow in patients with critical limb ischemia due to VEGF expressed by gene transfer in recent years has been reviewed in this article. Results Preclinical studies showed that VEGF can stimulate the development of collateral arteries in animals with limb ischemia, a concept called “therapeutic angiogenesis”, clinical results demonstrated that VEGF expressed by gene transfer can promote new vessel formation in patients with critical limb ischemia and improve significantly the prognosis for them.Conclusion VEGF gene transfer provide a novel treatment strategy for patients with critical limb ischemia, who neither had favorable response to phamarcological treatment nor were suitable for surgical reconstruction or revascularization.