Although recent phase II studies have demonstrated high antitumor activity in the treatment of advanced gastric cancer, no significant survival benefit has been clearly demonstrated yet, when compared with 5-FU alone. More recently, a number of new agents including irinotecan and S-1 have demonstrated significant activity against gastric cancer as single agent or in combination with other chemotherapeutic agents. A phase III trial of 5-FU alone versus irinotecan plus cisplatin versus S-1 alone in advanced gastric cancer patients will be initiated in Japan Clinical Oncology Group (JCOG) within a few months. These new regimens have a potential becoming a new standard chemotherapy for the treatment of gastric cancer. The patients with peritoneal dissemination has usually not yet evaluated and explored from clinical study because of risk of toxicity and having no measurable disease. A next randomized phase III trial comparing 5-FU alone with sequential methotrexate and 5-fluorouracil in patients with peritoneal metastasis will be initiated in JCOG next year. The development of molecular biology has demonstrated the molecular mechanisms of chemoresistance or chemosensitivity, as well as a number of molecular targets against cancer cells. To date, many molecular targeted agents are being evaluated in various stages of clinical testing. These advances may provide a possibility of tailor made treatment.