First-line therapy for metastatic gastric cancer has progressed from the use of 5-fluorouracil (5-FU) in the late 1960s through to an array of combination therapies such as cisplatin/5-FU, FAM (5-FU, doxorubicin, mitomycin), FAMTX (substituting methotrexate for mitomycin) and more recently ECF (epirubicin, cisplatin, 5-FU). Systemic chemotherapy has been shown to prolong survival compared with best supportive care alone, but the median survival for patients is still in the region of 9 months. This is because although gastric cancer is a chemosensitive disease with over 40% of patients showing a response, these responses are of short duration. Furthermore, it is difficult to consider one of the many frequently used regimens as a generally accepted standard for the treatment of these patients. Irinotecan (Campto ( R), CPT-11) is one of a group of new drugs showing activity in the treatment of gastric cancer, which include docetaxel, paclitaxel, oral fluoropyrimidines and oxaliplatin. Many phase II studies of irinotecan alone or in combination with cisplatin and/or 5-FU showed promising efficacy for the first and second line treatment. Eagerly awaited results of randomised phase III studies with irinotecan are expected to set new standards in the treatment of metastatic gastric cancer.