Critical limb ischemia is associated with a high risk of amputation and death. Several medical options have been tested on patients who cannot be revascularized surgically, but none has shown any effect on the amputation rate at 6 months.Gene and cell therapy intended to stimulate angiogenesis have been tested in phase I and II clinical trials. These innovative approaches appear both feasible and safe. Large randomized clinical trials are necessary to demonstrate their benefits and long-term safety.