Increasing evidence supports the investigation of chemotherapy in patients with non-small-cell lung cancer (NSCLC). Randomized studies in patients with stage IV disease have shown increased survival in chemotherapy-treated patients compared to best supportive care and indicate the ability of chemotherapy to alter the natural history of this disease. Randomized studies involving adjuvant and neoadjuvant chemotherapy have also shown encouraging results. These studies and results of recent pilot studies utilizing neoadjuvant chemotherapy and concomitant chemoradiotherapy indicate a potential benefit from the use of chemotherapy in patients with NSCLC and call for its continued intensive investigation in clinical trials.