A number of randomized clinical trials and meta-analyses now support the conclusion that combined modality regimens that include cisplatin (Platinol)-based chemotherapy improve survival in stage III non-small-cell lung cancer (NSCLC) more effectively than radiotherapy or surgery alone. Depending on the therapy, chemotherapy may play a cytoreductive role by eradicating distant micrometastases, a radiosensitizing role by improving local control, or do both. In general, sequential therapies in which platinum-based chemotherapy precedes thoracic radiation or surgery have improved outcome by affecting distant metastases. In contrast, concurrent chemoradiotherapy utilizing low-dose cisplatin improves survival by reducing local recurrence without an effect on distant failure rates. In view of these observations, chemoradiotherapy strategies that integrate both radiosensitizing agents and dose levels of chemotherapy that are effective against micrometastases may prove to be most efficacious. Since distant metastases remain the major site of failure, it is also likely that more effective chemotherapy or other systemic antitumor agents are necessary to increase the current level of response and survival. Fortunately, several new chemotherapeutic agents are highly effective against NSCLC as well as potent radiosensitizers.