Pancreatic cancer is highly aggressive and is a leading cause of cancer death in the Western world. Currently, there is no effective treatment for this disease; resection is only available to a small fraction of patients and has a marginal effect on overall survival rates. Chemotherapy and radiation also have very limited effects on patient survival. There is clearly a need for new approaches to treatment of such an aggressive disease. Gene therapy is of potential use in the treatment of cancer, and all currently available strategies are discussed with relevance to pancreatic cancer. A key to such strategy is specific delivery and selective gene expression in target cells. Current approaches include replacement of tumor suppressor genes, the use of antisense (AS) oligonucleotides, gene-directed enzyme prodrug therapy (GDEPT), and immunotherapy. The scene is now set for the next phase of development in clinical trials.