Treatment guidelines currently consider hepatitis B early antigen (HBeAg) seroconversion to be the end point of treatment with oral antivirals for HBeAg-positive patients. However, it is clear that with the high HBeAg relapse rate (both natural and after treatment) along with the high rate of mixed infection and the prevalence of HBeAg-negative disease, HBeAg status can no longer be considered the most useful end point of treatment or the signal to initiate therapy. Hepatitis B surface antigen (HBsAg) loss or seroconversion is associated with a favorable prognosis in both HBeAg-positive and HBeAg-negative disease and should be considered the test result that, combined with undetectable HBV DNA, will trigger treatment cessation.