Gene therapy comprises of introducing specific genetic material into target cells without producing toxic effects on surrounding tissue. Gene therapy is one of the recent advances in this field to deal with this obstacle with promising prospects. As an oral physician it is our responsibility to treat common oral premalignant lesions and conditions like leukoplakia and oral submucous fibrosis which have a definite malignant potential if timely and early diagnosis and treatment is not provided. Treatment options for recurrent or refractory oral cancers are limited. A Medline search was done including the international literature published between 1989 and 2013. It was restricted to English language articles and published work of past researchers including in vitro and in vivo studies. Google search on gene therapy was also done. Despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with oral squamous cell carcinoma has not significantly improved over the past several decades. A potential approach to the treatment of oral premalignant and malignant disorders is gene therapy.