The poor overall survival of lung cancer patients treated with conventional therapies (chemotherapy, radiation therapy, and surgery) mandate novel approaches to treatment. Two novel approaches to treat lung cancer include gene therapy and immunologic therapy. Both treatments have preclinical data suggesting potential clinical use. In gene therapy, the identification of specific genes critical to the development of carcinogenesis has offered the opportunity to target these genes or their products for treatment. One possible gene therapy strategy that has been pursued in phase I and II lung cancer trials is to replace nonfunctional tumor suppressor genes such as mutated or deleted p53 genes with wild-type p53 genes by adenoviral gene transfer (Ad-p53). Transduction of the tumors has been accomplished with direct intratumoral injection or broncheoalveolar lavage. These studies have identified a potential role for radiosensitization of previously radiation-resistant local tumors by combining Ad-p53 with radiation or possibly chemoradiation. Another novel strategy that may allow systemic treatment of lung cancers is immunologic therapies. Immunotherapies have focused on augmenting the immune response to cancer by passive strategies (e.g., antivascular endothelial growth factor) or active nonspecific (e.g., interferon), or by specific (e.g., anti-idiotype therapy) strategies. These novel strategies are currently in clinical trials and will potentially allow additional therapeutic options for patients resistant to conventional therapies.