Major advances in cancer control will be greatly aided by early detection for diagnosing and treating cancer in its preinvasive state before metastasis. Unfortunately, for pancreatic ductal adenocarcinoma (PDAC), which is the fourth leading cause of cancer-related death in the United States, effective early detection and screening are currently not available and tumors are typically diagnosed at a late stage, frequently after metastasis. Partly because of low sensitivity/specificity, existing biomarkers such as CA19-9 are not adequate as early detection markers of pancreatic cancer. Thus, a great need exists for new biomarkers for pancreatic cancer. This article focuses on recent developments in the identification of new serum protein biomarkers that are useful in the early detection of PDAC.