Lung cancer accounts for one-third of all cancer deaths worldwide. Once considered untreatable, lung cancer patients now have several different treatment options, and the potential for more effective therapies is promising. Clinical trials conducted during the past 25 to 30 years in the United States Cooperative Group System and throughout the world have defined the standard of care and made several initial treatment therapies possible. This article includes a summary of major findings of significant trials for varying disease stages; reviews major drug developments; and includes and a discussion of unanswered questions and trials currently underway that may provide the answers. Depending on the stage of disease, various therapeutic combinations can be effective in improving the time to progression, response, safety, and survival of lung cancer patients. Much has been accomplished on behalf of lung cancer patients. However, 80% to 90% of patients who develop lung cancer will die of their disease. Many questions remain to be answered, especially in the area of targeted therapies.