Gene therapy potentially allows local delivery and expression of cytokines, growth factors, and other mediators. In spite of increasing knowledge of the human genome, applications in clinical practice are only just beginning. The main limitations of effective clinical gene therapy are safety and low transfection efficiency. Saphenous vein grafts permit the transfection of the conduit ex vivo. This allows a variety of transfection techniques to be used, enhancing the transfection efficiency while limiting the risk of systemic complications. This review examines the potential mechanisms of gene delivery and genetic targets that may be applied to saphenous vein graft failure.