Pancreatic cancer (PC) carries the highest mortality rate of any cancer type. Although minor advances in chemotherapy have been made, the mortality rate has remained the same over the last several decades. Clinical trials examining therapies targeting the epidermal growth factor (EGFR), vascular endothelial growth factor (VEGF), specific mutated proteins such as K-ras, immunotherapy employing tumor-associated antigens, and biologic therapy such as TNFerade (GenVec, Inc., Gaithersburg, MD) have all failed to substantially improve survival. Pancreatic cancer is likely a heterogeneous disease; therefore, a personalized genomic approach offers the possibility to tailor treatment to the unique characteristics of individual patients and their tumors. Rapid advances in sequencing technology are decreasing the time and cost of obtaining this information to a clinically useful level. However, many challenges remain to be faced in applying this technology in the field of PC. Even if patients with PC could be identified early in the course of the disease, localizing the disease and treating it in a minimally invasive fashion will remain problematic. Ethical issues including patient discrimination and access to care will be particularly important in PC. As the field advances, validation, education of clinicians, and determining the true value and source of funding will be difficult. Although the era of personalized genomic medicine has arrived, it will certainly take many years to begin to realize its potential. It is to be hoped that this new approach will result in a significant improvement in the survival curve for patients with PC.