This update reviews the remarkable progression in several cardiovascular gene transfer domains. The first chemical gene therapy protocols to stimulate angiogenesis in ischemic myocardium are discussed and both the great expectations as well as remaining hurdle are highlighted. In experimental models of restenosis and heart failure gene therapy shows promising results. Important question regarding vector-related limitations and suboptimal in vivo delivery systems will require expeditious attention for gene therapy to become a more widely applicable option in cardiovascular diseases.