The incidence of peripheral arterial disease is rising and despite advances in clinical management, many problems remain unsolved. Better knowledge of the mechanisms and consequences associated with chronic muscle ischemia has opened the way for development of new treatment strategies, including therapeutic angiogenesis. Therapeutic angiogenesis is a promising technique based on experimental studies showing that growth factors or genes able to increase capillary density can be used to reduce the impact of muscle ischemia and increase blood flow to ischemic tissue. Enthusiasm for this technique has prompted numerous clinical trials with encouraging results, but data are still inconclusive. Optimal indications for gene therapy must be defined and further experimental progress is needed to respond to ethical issues. Therapeutic angiogenesis should be viewed as an adjunct to rather than as a competitor of current surgical revascularization techniques.