Patients with gastric adenocarcinomas have a poor prognosis. Because curative surgery is often impossible (metastatic disease) or extremely difficult (locally advanced tumors), and the majority of patients undergoing curative resection relapse, chemotherapy has been actively studied in gastric cancer. Many drugs have shown activity; however, single-agent chemotherapy failed to demonstrate increased survival benefit. Several combination regimens have been developed with high activity in locally advanced and metastatic disease. Among them are 5-fluorouracil (5-FU) plus high dose methotrexate plus doxorubicin (FAMTX), etoposide plus doxorubicin plus cisplatin (EAP), etoposide plus leucovorin plus 5-FU (ELF), and epirubicin plus cisplatin plus 5-FU (ECF). Although the response rates of these schedules are encouraging, the toxicity is considerable. Randomized trials comparing chemotherapy with best supportive care showed an increase in overall survival and in quality-of-life. Up to now adjuvant chemotherapy in curatively resected gastric cancer patients has failed to improve survival as compared with surgical controls. Phase II trials with preoperative chemotherapy have shown very promising results, but results of randomized trials should be awaited to judge the real value of this approach. At this moment it cannot yet be estimated whether preoperative chemotherapy does positively influence the resection rate and survival of patients with clinically resectable tumors.