The poor overall survival rates associated with non- small-cell lung cancer despite advances in chemotherapy, radiotherapy, and surgery mandate the search for novel approaches. Advances in gene transfer technology have allowed gene therapy strategies to develop that act in such a way as to stimulate the immune system, transfer "suicide" genes, inactivate oncogenes, replace tumor suppressor genes, and transfer pro-apoptotic genes. Clinical trials evaluating these possibilities have begun, and findings indicate that the transfer of tumor sup- pressor genes (wild-type p53) is feasible and has low overall toxicity. Subsequent clinical trials have begun to evaluate the clinical potential of these approaches in non-small-cell lung cancer.