A number of studies have demonstrated that preoperative chemotherapy (CTx) and combination radiochemotherapy (RTx/CTx) in patients with potentially resectable and locally advanced squamous cell esophageal carcinoma is feasible. In patients with potentially resectable tumors, neoadjuvant therapy followed by surgical resection has, however, so far not shown an increase in the resection rate, rate of complete macroscopic and microscopic tumor resections, i.e. R0-resections according to the UICC, or survival time as compared to patients who had surgical resection alone. In this situation a survival benefit, if at all, can be expected only in those who respond to preoperative therapy. At the present time preoperative CTx or RTx/CTx in patients with potentially resectable esophageal carcinoma must therefore be considered investigational and should not be performed outside the context of clinical trials. In patients with locally advanced esophageal carcinoma, neoadjuvant therapy markedly increases the rate of R0-resections and appears to prolong survival. Combined modality therapy in this context is, however, associated with a substantial perioperative mortality and morbidity. Open questions that have to be addressed by randomized studies include the role, extent and timing of surgical resection in the combined modality approach to patients with locally advanced squamous cell esophageal carcinoma. Research has to focus on preoperative staging modalities and the development of more effective and less toxic preoperative therapy regimen to improve identification of patients that might benefit from combined modality therapy and to more effectively combat systemic recurrences.