Despite surgical efforts and encouraging data of a few postoperative therapy trials, locally advanced gastric cancer is in need of the development of effective multimodal therapeutic concepts. Regarding preoperative therapy the goal is to raise the number of complete tumor resections (R0-resections) leading to an improved prognosis of the disease. Neoadjuvant therapy has the theoretical advantage of early destruction of distant micrometastasis with a consecutive reduction of tumor relapse outside the resection margins. The likelihood of R0-resections should be increased with the response of the primary tumor to neoadjuvant therapy. Neoadjuvant chemotherapy using platinum based regimens in gastric cancer has shown its activity in a number of phase II studies. Especially after response to chemotherapy the survival was significantly better after complete surgical tumor resection. The neoadjuvant use of a sequence of chemotherapy followed by radiotherapy before gastrectomy did result in a complete histopathological response in 20-25% of gastric cancer patients. This regimen seems to be promising, but there are still no long term results available. Parallel to the expected data from the first phase III studies the main impact of research in this field has to be focused on to the development of new and effective therapeutic agents and with accompanying identification of factors which are able to predict the response to neoadjuvant treatment.