Pancreatic adenocarcinoma remains a widespread and difficult disease to treat. Surgical resection offers the possibility of cure in a select few. However, most patients are not eligible, and conventional chemotherapy and radiation remain largely ineffective. Despite this, our understanding of the pathogenesis of the disease has advanced considerably over the past few decades. These findings provide the basis for the development of much needed new therapeutic modalities. Specifically, the application of new recombinant DNA technology and techniques to pancreatic cancer has yielded promising results. This paper reviews our current understanding of the molecular biology of pancreatic adenocarcinoma and its applications to the field of gene therapy. © 2004 Association of Program Directors in Surgery.