Gene therapy provides a promising approach for regeneration and repair of injured bone. Application of gene therapy has displayed increased efficiency in various animal models and preclinical trials in comparison with traditional bone grafting methods. The objective of this review is to highlight fundamental principles of gene therapy strategies in bone tissue engineering and solutions of their current limitations for the healing of bone injury. Vector types are debated for the repair of defected site due to demonstration of constraints and applications of the protocols. In recent years, the combination of gene therapy strategies and bone tissue engineering has highly gained attention. We discussed viral and non-viral mediated delivery of therapeutic protein by using scaffolds for bone tissue engineering. Although pre-clinical studies have showed that gene therapy has very promising results to heal injured bone, there are several limitations regarding with the usage of gene delivery methods into clinical applications. Choice of suitable vector, selection of transgene and gene delivery protocols are the most outstanding questions. This article also addresses current state of gene delivery strategies in bone tissue engineering for their potential applications in clinical considerations.