Lung cancer remains the most common cause of cancer related death. Although the primary goal of therapy is improvement in survival, improvement of symptoms, and quality of life are also important. Platinum-based chemotherapy has been shown to confer a modest but statistically significant survival benefit. Platinum-based therapy, however, has been associated with significant toxicity. Newer agents, such as gemcitabine, vinorelbine, paclitaxel, docetaxel, and irinotecan have been introduced into clinical practice. These agents have different mechanisms of activity and improved toxicity profiles. Combinations of these novel agents have been developed in an attempt to improve the toxicity profile and efficacy of the treatment of non-small cell lung cancer. This paper evaluates gemcitabine-based non-platinum combinations in the treatment of non-small cell lung cancer. Ongoing research evaluating the optimal dose, schedule, and combination is important in achieving improved outcomes in terms of survival and quality of life. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.