Based on results from extensive clinical research, interferon-alpha-2a (IFN-alpha-2a, Roferon-A, F. Hoffmann-LaRoche Ltd., Switzerland) and other interferons have been registered for the treatment of chronic active hepatitis B. The officially recommended dose regimen is 4.5 MIU (or 2.5 MIU/m2) thrice weekly for 6 months. To present guidelines for the optimization of treatment for individual patients, 3 major controlled trials from our worldwide research program with a total of 416 patients were reviewed in a meta-analysis. Before deciding whether to treat or not, the history, prognosis and chances of treatment success for a given patient must be carefully assessed. Liver histology and repeated quantitative measurements of markers for viral replication (HBV-DNA, HBeAg) and biochemical markers for liver disease such as ALT are valuable indicators. After the decision to treat, monthly quantitative measurements of these markers make it possible to monitor therapeutic success. Depending on the course they run, treatment can continue unchanged, be adjusted in dose or duration until a full response is achieved, or be terminated early in case of evidence of non-response.