Randomized trials demonstrated the significantly improved survival benefit of 5-fluorouracil (5-FU) based chemotherapy in patients with unresectable advanced gastric cancer (AGC) in comparison with best supportive care (BSC). However there is no chemotherapy considered worldwide to be the standard treatment for AGC and there is no consensus as to whether combination or single agent therapy is preferable. Therefore, 2 large Phase III studies JCOG 9912 5-FU vs TS-1 vs CPT + CDDP and TS-1 vs TS-1 + CDDP are now ongoing to establish an acceptable frontline standard for patients with AGC. We need to develop new agents and combination chemotherapy regimens to achieve greater survival benefit in AGC.