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Esophageal cancer is an aggressive malignancy with increasing incidence, and the prognosis of patients treated by surgery alone remains dismal. Preoperative treatment can modestly prolong overall survival. Preoperative chemotherapy or chemoradiation is the standard of care for resectable esophageal cancer (greater than clinical stage I and less than clinical stage IV). One of the challenges is to predict complete response in the surgical specimen from preoperative therapy and to avoid surgery in some patients but also predict ineffectiveness of preoperative therapy if the tumor is resistant and avoid such therapies altogether. In-depth understanding of the molecular biology could lead to personalized therapy, and in the future, clinical trials designed according to molecular features are expected. Here, we summarize preoperative treatment for esophageal adenocarcinoma and their potential.