Overall survival enhancement for patients with gastrointestinal malignancies is most likely to come from the integration of active systemic drug therapies into combined modality programs, applied in the surgical adjuvant or locoregional disease setting. Recent results of chemotherapy trials in advanced disease are discussed with emphasis placed on regimens that appear to be likely candidates for future early-stage disease studies. The ultimate success of this overall strategy depends heavily on identification of new active chemotherapeutic agents. meticulous disease-oriented phase II testing of all new agents in gastrointestinal cancers is critical to this effort.