Therapeutic angiogenesis based on the administration of growth factors with angiogenic activity allows enhancement of collateral vessels able to palliate insufficient tissue perfusion secondary to obstruction of native arteries. At present, this type of therapy is addressed to patients that fail to respond to conventional treatment (surgical or percutaneous revascularization). The most extensively investigated angiogenic growth factors are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). These cytokines can be administered either as recombinant proteins or as the genes encoding for these proteins. Both approaches have pros and cons that are under investigation in animal models and in clinical studies. Although clinical trials consist so far of small, often non-randomized series, preliminary results are promising. For example, administration of VEGF or FGF has been associated to objective evidence of increased tissue perfusion in patients with myocardial ischemia, and to a significant improvement of pain and ischemia in patients with peripheral arterial disease. Contrarily to expected, these interventions have been associated to scant adverse side effects, although larger clinical trials will be necessary in order to prove the safety and effectiveness of these interventions. Nevertheless, it seems clear that it is feasible to induce effective therapeutic angiogenesis in selected patients without significant associated toxicity.