For non-small cell lung Cancer (NSCLC) patients in good clinical condition (PS 0-1), Platin-based combination chemotherapy is currently recommended to prolong survival, prevent or reduce tumor-related symptoms, and maintain the quality of life. Nonetheless, the clinical availability of newer cytotoxic drugs has considerably increased the chemotherapeutic options for Platin-based chemotherapy and, at the same time, increased the difficulties in choosing the most appropriate regimen. These difficulties became especially clear when oncologists were confronted with the disappointing results from ECOG 1594, a study which tested four popular Platin-based combinations. Since no survival advantages could be shown by any of the four combinations used in ECOG 1594, one of the pertinent question seems to be whether, and in what form, a Platin-free combination regimen with newer agents should replace the currently recommended Platin-based therapy? A strong indication that non-Platin-containing regimens are not inferior came from at least two randomized trials. However, first results from EORTC 08975 -trial, did not confirm these observations, since the trend seems to be towards better results for the patients on Platin-containing regimens. A number of trials have shown that patients with PS >1 do not benefit from combination regimens. For these and for elderly patients, single agent therapy with newer cytotoxic agents may be for various reasons an attractive chemotherapeutic alternative for palliation. Several cooperative studies have proven that single agent therapy is superior to best supportive care. Vinorelbine was the first new agent tested in randomized, controlled trials in the elderly population, and was found to give statistically significant survival advantages in comparison to best supportive care only. As chemotherapy gains wider acceptance for advanced and early stage NSCLC, the need for an effective second-line chemotherapy is also growing. On the basis of two randomized, phase III studies, Docetaxel has recently become the first cytotoxic agent to be registered for second-line therapy in NSCLC. Both studies demonstrated that Docetaxel 75 mg/m2 given every 3 weeks significantly prolongs survival, and offers clinically meaningful benefits to patients who have an acceptable performance status.