Standard first-line chemotherapy for the majority of patients with advanced non-small-cell lung cancer (NSCLC) consists of platinum-based combination regimens including one of the newer-generation agents, such as gemcitabine (Gemzar), a taxane, vinorelbine (Navelbine), or irinotecan (Camptosar). Several effective regimens are available, the choice of which will depend on treatment goals, individual patient or disease factors, as well as physician preferences. This paper surveys randomized trials of many of the newer-generation chemotherapy combinations in patients with advanced NSCLC to examine several issues, such as which new-generation regimen to use, whether a platinum agent is needed, the optimal number of drugs in the combination, and treatment duration.