Adenocarcinoma of the esophago-gastric junction (AEG) represents an aggressive disease with poor prognosis. Surgery is the traditional mainstay of treatment for patients presenting with locally advanced disease, defined as transmural invasion with or without lymph node involvement. Surgical approach may differ, but the principal is to achieve wide mural clearance, negative margins, and perform an adequate lymphadenectomy. Although surgery is the primary modality that can cure patients, the majority of patients reveal recurrence leading to death within 2 years after resection. The incidence of locoregional relapse in most series and in phase II and phase III trials ranges from 25% to 60%, and 20-30% of these patients have no evidence of distant metastases. Median survival with surgery alone for localized disease remains poor, and ranges from 13 to 19 months with 5-year survival rates at best approximately 40%. To improve a long-term outcome in patients with esophageal and gastric cancers a combined modality therapy concept has been investigating for many years. The experience in a combined modality therapy for adenocarcinoma of the esophago-gastric junction have been extrapolated from studies on esophageal or gastric cancer, where the investigated population involved in part patients with AEG.