Gene therapy essentially consists of introducing specific genetic material into target cells without producing toxic effects on surrounding tissue. Advances over recent decades in the surgical, radiotherapeutic and chemotherapeutic treatment of oral cancer patients have not produced a significant improvement in patient survival. Increasing interest is being shown in developing novel therapies to reverse oral epithelial dysplastic lesions. This review provides an update on transfer techniques, therapeutic strategies, and the clinical applications and limitations of gene therapy in the management of oral cancer and precancer. We highlight the combination of gene therapy with chemotherapy (e.g., 5-Fluoracil) and immunotherapy, given the promising results obtained in the use of adenovirus to act at altered gene level (e.g., p53). Other techniques such as suicide gene therapy, use of oncolytic viruses or the use of antisense RNA have shown positive although very preliminary results. Therefore, further research into these promising gene therapy techniques is required to assess their true efficacy and safety in the management of these lesions.