No chemotherapy regimen showed a survival benefit better than 5-fluorouracil alone in a phase III trial for advanced gastric cancer in 1990s, and several new cytotoxic agents became available in late 1990s. Thereafter, a couple of phase III trials supported the substitution of infusional 5-fluorouracil by orally administered agents and the replacement of cisplatin by oxaliplatin in early 2000s. Furthermore, a substantial amount of information about the heterogeneity and the biological backgrounds of gastric cancer has been obtained from recent trials, and it is suggested that some cytotoxic agents would be well indicated. Trastuzumab has succeeded in showing a survival benefit for patients with Her-2 positive gastric cancer which accounts for about 10-20% of the cancer. This means that the door is opened to the new era of chemotherapy with molecular target agents and with individualization for advanced gastric cancer. The new approach in the development of molecular target agents, e.g., biomarker oriented strategy, for advanced gastric cancer should be studied in clinical trials in the near future.