For resectable esophageal cancer (stage II/II, non-T4), two courses of pre-operative chemotherapy with 5-fluorouracil (5-FU) plus cisplatin (CDDP) (FP) showed a significant survival benefit compared with post-operative chemotherapy with the same regimen in JCOG9907 trial (5-year survival rate; 60% versus 38%). On the other hand, the definitive chemoradiation therapy with FP (total 60Gy) resulted in a 5-year survival rate of 37% (JCOG9906 trial). At present, the standard treatment of resectable esophageal cancer is neoadjuvant chemotherapy with FP followed by surgery. Now neoadjuvant chemotherapy with triplet chemotherapy (docetaxel plus FP) and pre-operative chemoradiation therapy has been investigated in comparison with neoadjuvant FP. For locally advanced esophageal cancer (T4 and/or M1 lymph), JCOG0303 trial comparing standard dose of FP (5-FU 700 mg/m2/day, days 1–4, 29–32, CDDP 70 mg/m2 days 1, 29) with low dose FP (5-FU 200 mg/m2/day, 5 days per week, CDDP 4 mg/m2/day, 5 days per week, 6 weeks) concomitant with radiation therapy (total 60 Gy) showed equivalent survival curves (3-year survival rate; 28% versus 27%), no benefit of low dose FP. Thus, chemoradiation therapy with standard dose FP is recommended for locally advanced esophageal cancer. However, late toxic effects, especially in lung and heart, are a substantial problem. While radiation dose of 50.4 Gy is a global standard, it is expected that progression in radiation methods will reduce late toxic effects. For metastatic disease, FP is a standard chemotherapy, resulting in a response rate about 30% and median survival time of 7–8 months. Docetaxel and paclitaxel showed response rates of 30–40% in the second-line setting. Triplet therapy with taxane added to FP and molecular target agents such as anti-EGFR monoclonal antibody are expected to improve the efficacy.