Non-small cell lung cancer (NSCLC) is refractory to systemic chemotherapy, compared with small cell lung cancer. Until recently, only five drugs—cisplatin, vindesine, mitomyein, ifosfamide, and vinblastine—could produce overall response rates of 15% against NSCLC. However, recent efforts have contributed to the development of new drugs with activity against NSCLC, including irinotecan hydrochloride (CPT-11), paclitaxel, docetaxel, vinorelbine, and gemcitabine. Combination chemotherapy against NSCLC using these agents has demonstrated high response rates. In Japan, various combination chemotherapy and combined-modality regimens employing CPT-11 have been evaluated for their efficacy. Randomized controlled trials to establish new state-of-the-art treatments for NSCLC are ongoing.