The diagnosis of pancreatic cancer continues to produce fear in both patients and practitioners in large part owing to the likely incurability in all for whom the diagnosis is made. It is this reality that continually motivates the surgical and medical oncologists who endeavor to treat these patients. Currently, the cure rate for pancreatic cancer has improved only minimally, and the overall survival of patients remains dismal, with fewer than 5% of patients alive at 5 years and 92% of these patients dead at 2 years. This current treatment status has stimulated numerous studies endeavoring to understand the diverse mechanisms of cell growth in this tumor. Intensive investigative efforts have produced the understanding of new tumor suppressor genes such as DPC4 and an increasing understanding of tyrosine kinase receptors and signal transduction and their regulation of programmed cell death (apoptosis). Detection of these numerous genetic defects may give new insights and understanding of the highly chemo- and radioresistant nature of pancreatic cancer. These same findings also provide the basis for the development of new potential therapies for pancreatic cancer through gene therapy. This paper reviews the significant molecular biologic findings and their influence on the development of gene therapy strategies in the treatment of pancreatic adenocarcinoma.