Although the role of systemic chemotherapy has been established for the treatment of advanced gastric cancer, the prognosis of these patients remains poor, with a median overall survival of less than 1 year. Based on the results of several randomized Phase III trials, 5-fluorouracil continuous infusion plus cisplatin, with or without epirubicin, has become the global reference regimen for this patient population. However, treatment with fluorouracil infusion requires either frequent hospitalizations or the use of a central venous access device, harboring potential complications. Capecitabine, a tumor-activating oral prodrug of fluorouracil, may be more advantageous in terms of patient convenience, safety and efficacy. Two recent randomized Phase III trials have shown that capecitabine could replace infusional fluorouracil in cisplatin-based regimens. Furthermore, Phase II trials have shown that many other capecitabine-based doublet or triplet chemotherapy regimens incorporating newer cytotoxic agents are active and well tolerated. Many promising biological agents are now being tested in Phase III trials, incorporating capecitabine combinations as control arms, in patients with advanced gastric cancer.