Pancreatic cancer is one of the most aggressive and fatal malignancies, and is ranked as the third leading cause of cancer death at the European Union and North America. This chapter reviews the currently treatment of metastatic pancreatic adenocarcinoma. Single-agent therapy is an option for patients who are not fit or candidates for a more intensive first-line chemotherapy regimen. There is considerable heterogeneity in the survival of patients receiving second-line chemotherapy and we do not know how to predict which patients will benefit. BRCA 1&2 mutations, response rate 2,26-6,2 and colorectal cancer predisposition (deficient mismatch repair) have been associated with susceptibility to pancreatic cancer. Offering the opportunity of participating in a clinical trial and genomic testing are recommended at the National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines.