Although significant advancements have been achieved in periodontal therapy over the last decade, predictable regeneration of the tooth-supporting tissues is a challenge in periodontology and oral implantology. Recently, gene therapy, a new therapeutic approach for genetic and acquired diseases, has been applied for tissue bioengineering in multiple clinical situations, including the craniofacial complex, among them defects resulting from periodontal disease. The use of gene therapy vectors has enhanced the bioavailability and targeting of multiple growth and host immune factors to repair alveolar bone defects. Early pre-clinical studies utilizing both ex vivo and in vivo gene transfer strategies demonstrate the feasibility of using gene therapy for periodontal tissue engineering. This review highlights the current progress made in the field of periodontal regenerative medicine via gene targeting approaches.