This review highlights the current strategies being employed towards gene therapy of cancer. Conceptually, the most simple diseases to treat with gene therapy would be monogenic inherited diseases, such as hemophilia. However, the vast majority of current gene therapy trials are for treatment of cancer patients, due to the recognition of gene alterations in cancer and the critical need for improvement of cancer therapy. Gene-based therapies for cancer in clinical trials include strategies that involve immuno-therapy, induction of drug sensitivity in tumor cells or resistance to chemotherapy of critical host tissues, and compensation for oncosuppressor loss or ablation of oncogenes. Two broad approaches have been used to deliver DNA to cells, a series of viral vectors and the use of plasmid DNA vectors, which have different advantages with regard to efficiency of gene transfer, ease of production and safety. Examined objectively, many of the first studies in cancer gene therapy clinical trials have provided information of critical importance for the design of more efficient second-generation protocols. Gene therapy represents one of the most important developments in oncology, however, before this can be realized as standard treatment the technical problems of gene delivery and safety must be overcome. Here we focus on methods and strategies used to achieve cancer gene therapy and the current clinical trials.