The role of chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC) has been debated over three decades, but it is only relatively recently that chemotherapy has become a standard of care for this disease. In addition to prolonging survival, chemotherapy can palliate distressing symptoms. Concerns that the adverse effects of chemotherapy are likely to outweigh its benefits have largely not been confirmed by quality-of-life data reported among patients with good performance status. Platinum-based chemotherapy regimens in which cisplatin or carboplatin are partnered by a third-generation cytotoxic drug such as gemcitabine, paclitaxel or vinorelbine, have similar activity and efficacy, but differ in adverse effect profiles. Response rates of 30-40% should be expected with median and 1-year survival of 8-10 months and 30-40%, respectively. In the second-line setting chemotherapy with docetaxel has been shown to be significantly superior to best supportive care alone. In a recent trial that compared docetaxel to the novel antifolate, pemetrexed the response rates and survival rates did not differ, but the toxicity profile favored pemetrexed. Overall, these data demonstrate that progress has been made in the use of chemotherapy to improve survival in patients with NSCLC without increasing the incidence of further toxicity. In the past, the potential to survive 1 year was extremely small, whereas now many more patients reach this milestone as well as the 2-year point. However, a plateau has probably been reached with existing cytotoxic drugs and there is a general belief that the next significant advance in the treatment of NSCLC will come from the addition of drugs that target specific molecular pathways in sequence with standard chemotherapy regimens.