In the short time since the inception of gene therapy, significant advances have been realized. Although this progress has not realized definitive breakthroughs in the treatment of solid organ tumors, including pancreatic cancer, the hope is that advances will come with improved gene delivery systems and alternative approaches. The authors review the history of gene therapy, the current treatment strategies and delivery systems, the preclinical studies on its application to pancreatic cancer, and provide an up-to-date list of federally approved gene therapy cancer trials.