Various regimens of combination or sequential therapy using nucleoside/nucleotide analogues (NAs) and interferon-alfa (IFN-alpha) have been tried for the treatment of chronic hepatitis B. To date, combination therapy of two NAs and of IFN-alpha and NAs fails to achieve extra viral suppression. Sequential therapy with lamivudine followed by IFN-alpha seems to have better sustained virologic response. However, the long-term beneficial effect of using this approach remains to be defined.