Over the past decade, there has been a renewed enthusiasm to develop noninvasive serum markers or tests to assess the presence and severity of fibrosis in chronic liver disease. Although a single marker or test has lacked the necessary accuracy to predict fibrosis, different combinations of these markers or tests have shown encouraging results. However, inter-laboratory variability and inconsistent results with liver diseases of varying etiologies have made it difficult to assess the reliability of these markers in clinical practice. In this issue of the journal, Poynard et al. describe the "histological" response to lamivudine in patients with chronic Hepatitis B Virus (HBV) over a 24-month period using surrogate serum biomarkers (Fibrotest-Actitest, FT-AT) without corroborating histological data. Investigators found improvement in fibrosis and inflammation in 85% and 91%, respectively, despite the emergence of YMDD mutation in 41.5% of patients. The higher improvement rates reported in this study should be interpreted with caution for a number of reasons including the absence of data on virological response rates, corroboratory histological data, and data on the validity of FT to evaluate fibrosis in a longitudinal manner. Although FT has been studied extensively by the authors of the current study, to date there are only few independent studies. In addition to significant inter-laboratory variations, these studies have shown that significant fibrosis could be missed, or conversely significant fibrosis diagnosed in the absence of minimal or no fibrosis in about 15% to 20% of patients. We may be approaching a time when serum biomarkers may become an integral part of the assessment of patients with chronic liver disease, but published evidence suggests that these markers are not yet ready for prime time.