The incidence of distal esophageal adenocarcinoma and primary proximal gastric carcinoma has increased substantially in the past 15 years, particularly in North America and in some European countries. Patients with curatively resected cancer consistently have a 10 to 20% 5-year survival rate. Radiation therapy alone should not be recommended. Based on the Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group (ECOG) trial in patients with predominantly squamous cell carcinoma, chemoradiotherapy (fluorouracil [5-FU]/cisplatin + 50 Gy of radiotherapy) has been shown to be superior in this setting. The most active single agents against squamous cell carcinoma are cisplatin, 5-FU, bleomycin, paclitaxel, mitomycin, mitoguazone, vinorelbine, and methotrexate. The most active agents against adenocarcinoma include paclitaxel and probably mitomycin, mitoguazone, and cisplatin. To my knowledge, there is currently no effective postoperative adjuvant therapy (chemotherapy, radiation therapy, or both). Evidence that preoperative therapy can prolong survival of patients with potentially resectable carcinoma of the esophagus is lacking. Preoperative chemoradiotherapy can result in an approximately 25% complete pathologic response of the primary tumor. Preoperative chemoradiotherapy, however, results in substantial morbidity and even mortality. A recent single-institution, randomized study comparing surgery alone with preoperative 5-FU/cisplatin/vinblastine and concurrent radiotherapy demonstrated no difference in median survival (18 months). Nevertheless, combined-modality therapy holds promise. Multiple combined-modality strategies have been formulated and will be investigated in the next few years.