Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. There has been minimal progress with regard to cancer-specific outcomes in recent decades. Although effective therapies will undoubtedly change the natural history of the disease, effective biomarkers are a promising tool that will likely have a positive impact and will undoubtedly have an important role in the management of patients with pancreatic ductal adenocarcinoma (PDA) in the future. At present, serum CA-19-9 (carbohydrate antigen 19-9) is the only Food and Drug Administration-approved biomarker for PDA, and it has utility as a prognostic marker and as a marker of disease recurrence. There has been a recent explosion in the pancreatic cancer biomarker field with more than 2000 biomarker studies implicating thousands of informative genes as candidate biomarkers. In this review, we summarize the literature on CA-19-9 in PDA and highlight the most promising investigational biomarkers. Distinctions are made between diagnostic biomarkers (detection of disease), prognostic biomarkers (provide information on prognosis and recurrence pattern), and predictive biomarkers (predict treatment response).