The early success of coronary artery bypass grafting (CABG) is limited by disappointing long-term patency rates of autologous saphenous vein grafts. Because current pharmacological interventions have only limited impact on vein graft patency rates, there remains a clear clinical need for effective agents to prevent failure of vein grafts in the long term. Gene therapy in vein grafts has great potential as gene delivery can be achieved ex vivo at the time of cardiac surgery, allowing transgene expression to occur rapidly post-grafting within the acute phase of vein graft remodelling. A variety of therapeutic strategies have been tested in a range of preclinical models, although to date, these have not advanced to Inhuman trials, except in the setting of adjunctive angiogenesis for improved revascularization (phase 1). Clinical translation is warranted to investigate the potential of gene therapy to improve CABG patency rates in the long term.