Cardiovascular diseases are one of the main causes of mortality in Western countries. Gene therapy is emerging as a potential strategy for the treatment of cardiovascular diseases, such as peripheral arterial disease, ischemic heart disease, restenosis after angioplasty, vascular bypass graft occlusion and transplant-associated coronary artery disease. Since the initial experiments more than one decade ago, remarkable progress has been made in the field of gene transfer and human clinical trials are underway. In here we give an overview of available gene transfer strategies describing several delivery routes and currently used vectors in animal studies and clinical trials. Hereby we want to focus on new approaches including the potential combination of gene therapy with cell therapy and tissue engineering, gene silencing and recently developed techniques for targeting genes to the vascular wall and the myocardium.