Pancreatic cancer, one of the most frequently reported gastrointestinal tumors, has a 5-year survival of less than 5%. Despite representing only 2-3% of the total cancer incidence, it is the fifth leading cause of cancer death. This is because it is commonly only diagnosed at an advanced stage. Until recently the traditional therapy for patients with advanced disease was palliative 5-fluorouracil (5-FU)-based chemotherapy. However, the novel antinucleoside gemcitabine (Gemzar) has demonstrated a survival benefit over 5-FU, and an improvement in disease-related symptoms and quality of life in patients with advanced disease. This review presents an overview of the clinical studies of gemcitabine, either alone or in combination, with other chemotherapeutic agents and/or radiation therapy, in the treatment of these patients. A comparison of these studies is made with those using alternative treatment regimens. The data suggest that gemcitabine in combination with biomodulated 5-FU should be considered the standard palliative treatment to which other new drug combinations or combined modality chemoradiation regimens should be compared.