Cancer of the esophagus and gastroesophageal junction remains a virulent malignancy with an overall poor prognosis. Especially in the Western hemisphere, the incidence of adenocarcinoma is sharply rising. Over the last two decades, surgery has become the mainstay of treatment. Decreased surgical mortality and standardization of oncologic principles focusing on the completeness of resection are believed to be responsible for the improved 5-year survival rates, which are reaching > or = 30%. Until now, there has been no proven benefit from combined neoadjuvant treatment modalities using chemotherapy or chemoradiotherapy except for the subset of patients showing a complete response at pathologic examination. Further research should focus on new chemotherapeutic agents and the development of molecular markers that allow better identification of candidates for multimodality regimens.