In the early 1990s, a combination of 5-fluorouracil (5-FU) and cisplatin was widely adopted to treat advanced gastric cancer; however, no survival advantage over single-agent 5-FU was confirmed by the results of randomized trials conducted over a long period. Recently developed agents such as irinotecan, taxanes (docetaxel), and new oral fluorouracil (S-1) have yielded more promising results, with a response rate of over 50% and a median survival time of over 10 months in combination studies. These newer combination regimens were investigated in various randomized phase III studies to clarify if the newer-generation regimens provided a survival advantage over the older-generation regimens. Based on the findings of a large randomized study, S-1 has become standard in the adjuvant setting after D2 dissection curatively resected stage II and III gastric cancer. This article reviews the recent advances in gastric cancer chemotherapy, especially in Japan.