Postoperative adjuvant chemotherapy with tegafur-uracil has become the standard of care for patients with completely resected stage I adenocarcinoma according to the positive result from phase III trial conducted in Japan. The effectiveness of tegafur-gimeracil-oteracil potassium in advanced non-small cell lung cancer (NSCLC) is now under investigation in a phase III trial in the first-line treatment in combination with platinum agent as well as in second-line treatment as monotherapy. The evidence of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) such as gefitinib and erlotinib was first confirmed as the second-line treatment for non-selective patients with advanced NSCLC. However, now it is essential to examine some active EGFR gene mutations such as exon 19 deletion or L858R in exon 21, the novel predictive factor for high efficacy of EGFR-TKI, in terms of the risk-benefit balance. For patients with EGFR-mutated advanced NSCLC, the first-line treatment with gefitinib had achieved a significant prolongation of progression-free survival compared with standard platinum doublet chemotherapy in a few phase III trials, and became a new standard of care. Gefitinib is highly effective for patients with advanced NSCLC with EGFR mutation even if their performance status is poor, although one should always pay careful attention to fatal interstitial lung disease.