In the last years peginterferon alfa-2a became one of the drugs of choice in the treatment of chronic hepatitis B. Its advantage is the possibility to reach the sustained response to the treatment with defined duration and a relatively low relapse risk after its discontinuation. In comparison with lamivudine a better efficacy was proven in HBeAg positive and HBeAg negative chronic hepatitis B as well. The recent observations confirmed also long time duration of the achieved response to this treatment. Peginterferon alfa-2a can be considered as a drug of first choice in the treatment of chronic hepatitis B above all in patients of young or middle age with a compensated liver disease. Its disadvantage remains the occurrence of side effects and the impossibility of use in cases of decompensated liver disease or in patients with some other serious diseases.