Circulating tumor DNA, circulating tumor cells and tumor-related exosomes may offer new opportunities to provide insights into the biological and clinical characteristics of a neoplastic disease. They represent alternative routes for diagnostic and prognostic purposes, and for predicting and longitudinally monitoring response to treatment and disease progression. Hence, circulating biomarkers represent promising noninvasive tools in the scenario of pancreatic cancer, where neither molecular nor clinical predictors of treatment benefit have been identified yet. This review aims to provide an overview of the current status of circulating biomarker research in pancreatic cancer, and discusses their potential clinical utility to facilitate clinical decision-making.