In critical limb ischemia, the aim of the treatment is to increase the arterial blood flow in the affected limb in order to relieve pain, heal trophic lesions, and avoid amputation. In patients in whom revascularization is not possible, medical treatment can occasionally be considered although it may not prevent limb loss in many patients. Medical strategies include the use of antalgics frequently opioids, antiplatet agents and prevention of venous thromboembolism. Selected patients may benefit from intravenous prostanoids, although their efficacy is unconstant. Maintenance of the bed in a dependant position may increase blood perfusion in the affected limbs. Gene and cell therapies, although promissing strategies, are currently evaluated in large clinical trials.