Interferon treatment of hepatitis B and C virus (HBV, HCV) infections has been hampered by overall initial response rates of < 50%, a relapse rate that is > 50% for patients with chronic HCV, and rare responses in individuals with chronic HBV who are immunosuppressed or immunologically tolerant to the HBV. Because of these difficulties, the efficacy of other therapeutic agents is being vigorously explored. Among the immunomodulatory agents being evaluated, thymosin appears to be a promising new therapy for HBV. Results from an ongoing multicenter trial evaluating thymosin are expected next year. A variety of nucleoside analogues with antiviral activity against the HBV have also been identified. Several of the more active agents deserve further study in clinical trials. In chronic HCV infection, only interferon therapy has been extensively studied. Ribavirin alone may have some value, but its precise role in the treatment of chronic HCV will require additional testing. Interferon therapy for patients with chronic HBV or HCV infection represents an important first step in the treatment of these disorders. In the absence of an ideal antiviral agent, however, combinations of the available antiviral and immunomodulatory agents or synergistic combinations of antiviral agents need to be studied in order to achieve better therapeutic responses.