Nonunions and delayed unions are among the more challenging clinical and surgical entities an orthopaedic surgeon must manage. Effective strategies that address these complex problems are in need and gene therapy represents a potential therapeutic option. Among the many properties that bone morphogenetic proteins (BMPs) possess, their potent osteoinductive effects make them attractive growth factors for use in gene therapy to address large bony defects. Gene therapy enables a sustained production of BMP to be achieved at specific sites of interest and represents a significant advantage over protein-delivery based systems. Viruses are effective vectors for delivering BMP cDNA because they are designed to efficiently infect cells and transmit genetic material. However, safety concerns such as immune system activation and insertional mutagenesis represent drawbacks that may limit their clinical efficacy. Nonviral vectors are emerging as attractive candidates for gene delivery since they avoid many of the safety issues seen with viral vectors but have lower genetic transfer efficiency. A wide variety or preclinical studies of bone regeneration using BMPs have demonstrated the efficacy of both in vivo and ex vivo gene therapy techniques and these will be explored in this review article.