This opinion piece evaluates the degree of readiness of 13 candidate biomarkers or panels of biomarkers for the early detection of hepatocellular carcinoma (HCC), or for the staging of liver fibrosis. As candidate biomarkers for the early detection of disease are identified, it is important to understand where they are in the developmental pipeline and how they might be employed. HCC is a growing public health problem, and its early detection is believed to be important in its management. Current detection methods are limited in usefulness or practicality, and there is a need for better methods to diagnose liver disease. Therefore, a number of candidate biomarkers, considered to be attractive because of their advanced stage of development or inherent scientific value, were evaluated for specificity and sensitivity for detection of liver disease. Study design, confirmatory evidence and assay practicality associated with each of the biomarkers are considered. The comments in this review reflect the authors' opinions and are based on a recent workshop convened by the Hepatitis B Foundation of America and the US National Cancer Institute's Early Detection Research Network. It is emphasized that only a selected set of biomarkers was considered; thus, this review is not comprehensive and not intended to review all candidate HCC biomarkers.