Lung transplantation has become a well-established management for many end-stage pulmonary diseases; however, the same success has not been achieved as with other solid organ transplants. Despite substantial improvements in organ preservation and the perioperative management of lung transplant recipients, ischemia-reperfusion injury, acute rejection, and chronic rejection persist. Severe ischemia-reperfusion injury affects as many as 20% of lung transplant recipients, prolongs mechanical ventilation, and may result in hemodynamic compromise. Acute rejection is the most common risk factor for bronchiolitis obliterans, a manifestation of chronic graft rejection, which ultimately progresses to graft failure. Gene therapy is a promising therapeutic option for these transplant-related injuries. Potential targets include donor and recipient, with a host of available delivery options and gene constructs. This review addresses the challenges of gene therapy and reviews its experimental progress in lung transplantation.