Non-platinum combination regimens have been developed for advanced non--small cell lung cancer using the novel and active agents docetaxel, gemcitabine, vinorelbine, and irinotecan. The aim of these combinations is to equal or exceed the survival benefits achieved with cisplatin doublets while minimizing toxicity. Of the docetaxel-based combinations, gemcitabine has been the most extensively studied. In a 317-patient randomized trial, docetaxel plus gemcitabine achieved a response rate of 34%, similar to the 32% response rate seen in patients randomized to docetaxel plus cisplatin. One-year survival rates were 38% and 42%, respectively. While being equally active, the docetaxel/gemcitabine combination was associated with significantly less neutropenia and gastrointestinal adverse events than the cisplatin-containing regimen. Phase II trials of docetaxel plus vinorelbine have reported response rates of up to 51% and 1-year survival in up to 60% of patients without significant peripheral neuropathy. Docetaxel plus irinotecan is also active in advanced non--small cell lung cancer and has shown similar efficacy to docetaxel plus cisplatin in a randomized trial. The adverse event profile of docetaxel/irinotecan is different from that of cisplatin-based regimens. Both non-platinum and platinum combination regimens have an important role to play in the treatment of non--small cell lung cancer. Semin Oncol 28 (suppl 9):15-20.