Despite numerous phase-II and phase-III studies investigating neoadjuvant treatment in esophageal and gastric cancer, the value of multimodal therapy in these tumors is not clearly defined yet. One reason are the different study entry criteria and different staging modalities in the investigations published so far. Concerning esophageal cancer, neoadjuvant chemotherapy does not yet have a definite role after several phase-III studies. It may be that this treatment should only be inaugurated in innovative protocols. Furthermore, in esophageal cancer it is proven that chemoradiation is superior to radiation alone in the neoadjuvant setting. Following neoadjuvant chemoradiation, there is a distinct trend in favor of multimodal therapy. In the case of locally advanced squamous cell carcinoma of the esophagus, neoadjuvant chemoradiation offers 30%-60% of the patients the possibility for a complete resection (UICC-R0); however, this is accompanied by increased postoperative morbidity and mortality. In gastric cancer, neoadjuvant chemotherapy is still an experimental approach. Intraperitoneal chemotherapy has failed to show any benefit in Western trials. Clinically related research is concentrating on the problem of distinguishing responder from non-responder at the beginning of the therapy. First results indicate that with molecular markers, response might be predicted before therapy. Using 18-FDG PET, it could be possible that the response can be recognized after only 1 week of treatment, opening the door to early response evaluation. New therapeutics like monoclonal antibodies for adjuvant therapy, which is again under discussion in gastric cancer, are only in phase-I studies.