Despite improvements in surgical care and locoregional therapy, the prognosis of patients with pancreatic cancer has seen little improvement over the last several decades. It is difficult to diagnose pancreatic cancer at its earliest stages when it is amenable to cure by surgical resection because it is too small to produce symptoms in the affected patient. Recent improvements in radiographic modalities aimed at earlier detection and extent of cancer spread have enabled the clinician to provide the most efficacious treatment regimen possible. Nevertheless, pancreatic cancer is very aggressive locally and frequently metastasizes to the liver and peritoneum. New strategies are necessary to treat pancreatic cancer and gene therapy offers hope in this regard. Many studies have revealed the promise of gene therapy in the treatment of pancreatic cancer in rodent models. Early clinical trials are ongoing to evaluate the success of these gene therapy regimens in humans. In this article we review the gene therapy strategies currently employed in the fight against pancreatic cancer, including antisense strategies, gene-directed prodrug activation therapy, promoter gene strategies, and oncolytic viral therapy.