Development and testing of antifibrotic agents for the treatment of chronic hepatitis C have generally been targeted toward hepatic stellate cells, transforming growth factor-beta, the inflammatory response, or extracellular matrix accumulation. Although several agents such as interferon-gamma, long-term pegylated interferon, and caspase inhibitors have been studied, none have proved to be effective to date. There is a clear need for drugs that inhibit or reverse hepatic fibrosis as these would be immediately applicable to patients for whom antiviral therapy has failed or who have contraindications to antiviral therapy such as those with decompensated liver disease or renal failure. A major impediment in the development of new drugs in this field has been the inability to identify appropriate histologic or clinical end points within a reasonable period of study. Progress on providing suitable end points to therapy will then promote the development of newer agents.