The report of the 1997 National Institutes of Health Consensus Development Conference on hepatitis C endorsed pretreatment liver biopsy. We revisit the following questions: Does liver histology help determine the urgency of, and predict the likelihood of response to, antiviral therapy, and can surrogate markers supplant histological assessment? Because the rate of progression of chronic hepatitis C is influenced by baseline histological grade/stage, patients can be stratified into those with moderate to severe hepatitis, who merit imminent therapy, and those with mild hepatitis, in whom therapy can be postponed until more effective/tolerable treatments become available. Less advanced baseline histology has been shown to be an independent predictor of responsiveness to antiviral therapy. Although the predictive value of biopsy is insufficient to withhold therapy from patients with advanced fibrosis, baseline biopsy helps gauge expectations for the outcome of therapy. Reports have been published recently suggesting that laboratory markers can predict distinctions between low-grade fibrosis and therapy-indicating septal fibrosis/cirrhosis. These indices, however, are insufficiently reliable to predict histological distinctions in populations with varying prevalences of fibrosis/cirrhosis or to provide anything more than broad qualitative distinctions, far short of the potential information in a liver biopsy. For most patients, the value of pretreatment liver biopsy outweighs its risks, provides information about the urgency of treatment, and should be retained. Studies to identify noninvasive laboratory markers of histological activity and stage, especially genetic predictors of accelerated disease progression, command a high priority. (HEPATOLOGY 2002;36:S152-S160).