Gene therapy has a potential to provide highly selective, curative cancer treatment without systemic toxicity. Adenovirus-based cancer gene therapy is a promising, novel approach for treating cancer resistant to established treatment modalities. Unfortunately, however, the efficacy of first generation adenoviruses was low and data from clinical trials were disappointing. Therefore, the development of tropism-modified, tumor-targeted vector systems is a critical issue in further developing the cancer gene therapy approach. At the same time, advances in our knowledge of cancer cell biology have led to the development of specific molecular-targeted antibodies. Recent developments of the gene delivery system include the successful use of bispecific antibody or adaptor protein to adenoviral vector and tumor related antigens. In this article, we summarized recent targeting strategies for the cancer gene therapy, including our study in which we developed a genetically modified adenovirus incorporating an IgG Fc-binding motif to bind monoclonal antibody for selective gene delivery to cancer cells.