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Biomarkers for Hepatobiliary Cancers. The clinical management of primary liver cancers such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) has significantly changed in the last 3 years. The introduction of systemic therapies, including immune-based therapies and biomarker-driven therapies, has significantly improved survival, particularly in patients at advanced stages of disease. Survival is still poor, and projections from the World Health Organization underscore the need to improve outcomes in these patients. Biomarkers have emerged as powerful tools for the diagnosis, prognosis, and prediction of treatment responses to improve patient stratification and maximize clinical benefits. Recent advances in understanding the molecular alterations of HCC have not yet translated into biomarkers. Some reasons for the lack of progress are the absence of druggable mutations in the majority of liver cancers and the significant heterogeneity of the disease. In contrast, several therapeutic targets have been identified in CCA, and biomarker-driven therapies are currently under evaluation in phase 2/3 clinical trials. Here, we summarize the status on biomarker development for HCC and CCA.