Critical limb ischemia is the end stage of peripheral arterial occlusive disease, with a deep impact in patient's quality of life. In some patients, there is no revascularizing treatment options, that determines major limb amputation in a high percentage of patients, not only for uncontrolled limb pain but also for complications of the trophic lesions. In the last years, several studies have shown the possibility to increase the perfusion in the ischemic tissue, by recombinant proteins, gene therapy or cellular therapy, all of them known as therapeutic angiogenesis. Several good results have been published but the way of treatment, doses and possible adverse effects still lack definitive conclusions. Randomized comparative studies should be carried out to determine the best treatment option.