Spontaneous loss of hepatitis B e antigen (HBeAg) followed by seroconversion to anti-HBe usually coincides with normalization of serum alanine aminotransferase (ALT) levels, reduction in HBV DNA in serum (< 1 × 106 copies/mL), and a marked reduction in hepatic inflammation. Licensed antiviral therapies are the interferon (IFN) alphas and the nucleoside analogue lamivudine. Both drugs enhance the rate at which HBeAg seroconversion takes place and thus reduce progression of disease. These therapeutic agents are ineffective if given when there is no ongoing hepatitis (i.e., normal ALT), and their efficacy is greatest in individuals with the most active disease. The effectiveness of these two classes of drugs is similar, and it is possible that the two therapies combined are more effective than monotherapy with either drug. A high side-effect profile and the high risk of further morbidity when given to patients with decompensated disease limit the use of IFN-α. When prescribing lamivudine, drug resistance that increases with duration of therapy and the potential risk of a severe flare of hepatitis with sudden cessation of therapy, probably greatest in patients with cirrhosis, are realistic concerns. Both patient and physician need to recognize the need for close monitoring both during and after cessation of any antiviral therapy for hepatitis B.