The field of gene therapy is still in its infancy, but significant accomplishments have been achieved. The ability to transfer genes safely and successfully into animals and patients clearly has been established. It is highly likely that in the near future, gene therapy will be shown to have clear therapeutic efficacy in diseases such as the treatment of hemophilia (using adeno-associated virus vectors) and the stimulation of angiogenesis in peripheral vascular disease and myocardial ischemia. Although only Phase 1 cancer gene therapy trials for thoracic malignancy have been conducted (usually in patients with large tumor burdens and at submaximal doses), there are some hints of efficacy at higher doses of vector in trials for localized malignancy. The studies reviewed in this article demonstrate the first attempts to use gene therapy vectors for lung cancer and mesothelioma. Although none of the diseases studied was "cured," valuable lessons have been learned from these trials, especially in defining the challenges of relatively inefficient and transient delivery of transgene in vivo. Using this knowledge, the second phase of gene therapy research has begun, with a strong focus on developing improved vector technology. Given the progress so far, there is little doubt that gene therapy will become a key approach for the treatment of thoracic malignancies in the near future.