Esophageal cancer, an uncommon, but highly virulent malignancy in the United States, will be responsible for nearly 14,000 deaths in the year 2005. The prognosis for patients who have adenocarcinoma of the distal esophagus and gastroesophageal junction and who are treated with the standard approaches of surgery or combined chemoradiation therapy is poor. Recent clinical trials have evaluated the use of preoperative chemotherapy followed by surgery, combined concurrent preoperative chemoradiotherapy followed by surgery, or definitive chemoradiotherapy alone without surgery. This article focuses on recent advances in the use of combined modality therapy in adenocarcinoma of the esophagus and gastroesophageal junction.