Pancreatic cancer continues to be a challenging therapeutic problem, with approximately 28,000 deaths annually in the United States. Most studies of single-agent or combination chemotherapy in the treatment of patients with advanced adenocarcinoma of the pancreas have documented low response rates and little reproducible impact on patient survival or quality of life. However, the recent success of gemcitabine in patients with locally advanced and metastatic pancreatic cancer suggests that systemic therapy can have a beneficial effect on the natural history of this disease. Also, the rapidly evolving understanding of the molecular biology of pancreatic cancer may contribute to the development and use of targeted therapies with novel agents for even more effective treatments in the near future.