Pancreatic ductal adenocarcinoma is one of the most common causes of cancer death in the developed world. Long-term survival is currently only achieved through surgical resection. Most patients have locally advanced or metastatic disease at the time of diagnosis and are therefore not amenable to resection, whilst chemotherapy and radiotherapy are by and large ineffective. Gene therapy offers an alternative to current adjuvant strategies. With approximately two-thirds of all gene therapy trials worldwide directed at cancer, the gene therapy approaches that are currently being explored for pancreatic cancer are specifically examined. Gene delivery systems, genetic targets, and combined gene delivery with chemotherapy are discussed in the context of pancreatic cancer treatment.