In patients with typical chronic hepatitis B (HBsAg, HBeAg, HBV-DNA-positive), treatment with interferon-alpha must be carried out for 4-6 months on an alternate-day basis and dosage should be not less than 5 million units/square meter of body surface. The therapeutic response (i.e., clearance of replicative markers, transaminases normalization, histologic improvement) is achieved in about 40% of treated patients and the long-term beneficial effect is maintained in about 90% of them. Oriental HBV carriers, children, immunodeficient and highly viraemic patients are less likely to respond. Patients given combinations therapy (with steroids, antivirals, stimulators of the immune system) do not appear to gain more benefit from the association in comparison with treatment with interferon alone. Side-effects are usually minor (flu-like symptoms), but in a minority major adverse events have also been reported. In conclusion, interferon-alpha is effective in inhibiting viral replication but new therapeutic regimens and a better selection of patients are needed in order to induce persistent remissions and to reduce the cost benefit ratio.