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Since the first M. D. Anderson Solid Tumor Oncology Series volume on pancreatic cancer, there have been major advances in our understanding of molecular events which underlie pancreatic cancer development, both in the sporadic and inherited forms. We have seen the development of the first mouse models that accurately recapitulate features of the human disease. Several landmark clinical trials in both resectable and metastatic pancreatic cancer have been completed, raising new questions about the standard of care in this disease. Finally, the era of targeted biologic therapies has engendered new excitement about the prospects of more rapid progress in understanding and successfully treating this dreadful disease. Therefore, it is an appropriate time to review these important advances and outline areas of controversy and question in pancreatic cancer biology and treatment.