Lung cancer, which is the leading cause of cancer mortality, remains a significant health-care problem among men and women in the United States, despite an overall 20-year decline in the incidence of cigaratte smoking. Non-small cell lung cancer (NSCLC) comprises 75 to 80% of all lung cancer cases. The metastatic nature of this disease has been responsible for the poor survival statistics reported to date and emphasizes the need for effective systemic treatment. Prior to 1993, attempts to identify new chemotherapeutic agents and combinations with activity against NSCLC met with little success. Recently, however, several new compounds and classes of compounds have offered some hope for at least small improvements in response and survival while being relatively well tolerated in patients with this disease. This article presents current findings for some of these agents, including the taxanes paclitaxel and docetaxel, the topoisomerase inhibitors irinotecan and topotecan, and the novel pyrimidine analogue gemcitabine. In addition, the University of Southern California/Norris Cancer Center experience with the combination of carboplatin and paclitaxel is presented.