For more than ten years standard therapy of chronic hepatitis B was limited to interferon-a and lamivudine. Interferon-a is known to have several adverse effects, while the use of lamivudine is associated with HBV (hepatitis B virus) mutations. New nucleoside/nucleotide analogues have been registered during the last few years. New antiviral agents with different mechanisms of action than that of nucleotide/nucleoside analogues should be used in the future to achieve the optimal goal of therapy: the total eradication of HBV infection.