Although extended surgery plus systematic lymphadenectomy may improve the prognosis of patients with stage II/IIIa (UICC classification) tumors, there is no doubt, that the results of surgery of gastric cancer have reached a plateau. An improvement of the current situation can be expected at best by additional treatment modalities in order to reduce local recurrences and distant metastases. For locally advanced gastric cancer (LAGC), which includes approximately two-thirds of patients with locoregionally confined tumors, preoperative chemotherapy represents a promising approach. In surgically or clinically staged inoperable LAGC, approximately half of the patients underwent complete (R0) resection after downstaging induced by active modern chemotherapy. The long-term survival of these patients appears to be about 20%. Well designed randomized studies, however, comparing surgery alone versus preoperative chemotherapy, should be undertaken in LAGC. In view of the high local recurrence rate being observed in published preoperative chemotherapy trials, the inclusion of radiotherapy (intraoperative radiotherapy, simultaneous chemoradiotherapy) or intraperitoneal chemotherapy should be considered for future investigations. In more early stages, curatively resected, adjuvant chemotherapy has no proven impact so far. Whether this will change with the use of more active chemotherapy or better timing of adjuvant treatment remains to be seen. Neoadjuvant chemotherapy has proven to be feasible and active also in potentially resectable tumors. Therefore, preoperative chemotherapy appears to be an attractive tool for clinical investigations also in earlier stages of gastric cancer.