Studies on neoadjuvant therapy of esophageal cancer showed that not either preoperative chemotherapy or radiotherapy lead to a significant improvement of prognosis. However, two prospective studies showed a significant prognostic improvement after neoadjuvant combined radio/chemotherapy. Most treatment protocols include a radiation with 30-45 Gy and a simultaneous therapy with Cis-Platin/5-Fluorouracil. As an increase of perioperative morbidity and mortality has to be expected through this treatment, a careful selection of patients is necessary. Several studies have shown that mostly patients with good response benefit from this neoadjuvant therapy. The clinical response evaluation is difficult and response is best proved by classification of the histomorphologic regression of the tumor. For future research, predictive response analyses based on molecular biologic and immuno-histochemic techniques are of great importance and first differentiations by biomarkers have been detected.