Traumatic bone defects and nonunion represent a significant source of morbidity and socioeconomic burden in trauma patients. The treatment of these conditions is currently hampered by inadequate therapies. This has prompted a new era of investigation into biologic therapies for augmenting fracture healing. Within this body of research, gene therapy has arisen as a novel and effective method of delivering therapeutic proteins at a site of desired bone regeneration. Gene therapy has shown tremendous potential in preclinical studies of fracture healing, but to date, no clinical trials have occurred. This article reviews the scientific basis for gene therapy in fracture healing, provides an overview of important preclinical studies that have been performed to date, and discusses the current barriers and future directions of gene therapy as it applies to fracture healing.