Advanced gastric carcinoma remains an incurable disease with a median survival of 6 to 9 months, and available therapeutic approaches are predominantly palliative. In small controlled trials, systemic chemotherapy has improved survival and quality of life of patients with advanced gastric carcinoma when compared with best supportive care. Patients with good performance status (Zubrod < or = 2), low tumor bulk, and good organ function are most likely to benefit from chemotherapy or combined-modality therapy. There is no generally accepted standard chemotherapy for advanced gastric carcinoma. Fluorouracil-and/or cisplatin-based combinations are often employed. Recently, several new classes of drugs have demonstrated activity against advanced disease. These include the taxanes (paclitaxel [Taxol] and docetaxel [Taxotere]), camptothecins (irinotecan [Camptosar], and flurouracil prodrugs (second-and third-generation agents, such as UFT [uracil and tegafur] and S-1). Early results with either single-agent therapy or combinations of new agents (irinotecan, paclitaxel, and docetaxel) and more conventional agents (cisplatin [Platinol] and fluorouracil) are encouraging. Several of these results need to be confirmed and eventually studied in well-designed, phase III trials. Similarly, a number of new combinations may be used in the future as preoperative therapies for gastric carcinoma. Nearly all of the new agents have radiosensitizing properties. This affords another opportunity to investigate new chemotherapeutic agents in conjunction with radiation therapy in patients with locoregional gastric carcinoma.