Transfer of the cDNA coding for angiogenic factors represents a novel and promising approach to induce therapeutic angiogenesis and enhance blood flow to ischemic tissues which cannot be revascularized otherwise. This review will focus on therapeutic angiogenesis based on gene transfer techniques for the treatment of myocardial and limb ischemia. The experimental studies demonstrating the angiogenic effect of recombinant growth factors in animal models and in humans, as well as the most promising methods for gene transfer, will be described. Further, gene transfer studies to induce therapeutic angiogenesis will be reviewed to identify critical questions that still need to be answered before gene therapy with angiogenic factors may be considered for routine clinical application.