Gene therapy presents a novel approach to the treatment of challenging bone loss problems. Recombinant, osteogenic growth factors are now available to enhance bone repair, particularly in those applications related to the treatment of fracture nonunions and the enhancement of fusion of the spine. However, there is concern that a single dose of an exogenous protein will not induce an adequate osteogenic signal in many patients, particularly in those cases where there is compromise of host bone and the surrounding soft tissue. Transfer of genes encoding osteogenic proteins has the potential to overcome the delivery problems associated with the use of the proteins themselves. Bone healing is an attractive application for gene therapy, because long-term protein production is not necessary for many bone repair problems. Therefore, the development of gene therapy strategies to treat bone repair problems promises to be easier than the application of gene therapy to treat chronic diseases. The purpose of this review is to highlight the advantages, disadvantages and clinical potential of various gene therapy strategies to enhance bone repair.