OBJECTIVE: To review the systemic chemotherapy regimens for pancreatic cancer. DATA SOURCES: Medline and non-Medline literature search (1966-1999). STUDY SELECTION: The following key words were used: pancreatic carcinoma; chemotherapy; antineoplastic agent; fluorouracil; gemcitabine. DATA EXTRACTION: Reports of phase II studies, randomised controlled studies, and preclinical studies were reviewed. DATA SYNTHESIS: Less than 20% of patients are suitable candidates for surgery; for the remainder, palliative chemotherapy is of only marginal benefit. Combining fluorouracil with folinic acid or interferon has not led to any significant improvement in tumour response or the patient survival rate. The early encouraging results with combination chemotherapy have not been confirmed in subsequent controlled studies. New approaches include immunotherapy and novel cytotoxic drugs. In vitro studies of monoclonal antibodies have shown promise but have failed to show clinical efficacy. Recently, gemcitabine has been shown to be more effective than fluorouracil in delivering pain relief and reducing disease-related symptoms. CONCLUSION: Systemic chemotherapy is generally ineffective in increasing the survival time of patients with pancreatic cancer. Future clinical investigations concerning treatment should focus on gemcitabine-based combination chemotherapy or combined modality treatment with radiotherapy.