The treatment paradigm of chronic hepatitis B (CHB) has been transformed by the introduction of nucleoside analogue (NA) therapy. Long-term NA therapy can suppress viral replication, improve liver histology, and reduce the risk of liver-related complications and mortality. For the large majority of CHB patients, NAs need to be taken long-term, since the occurrence of hepatitis B surface antigen (HBsAg) seroclearance, the established treatment endpoint of CHB, is a rare event. Nonetheless, once HBsAg seroclearance is achieved, virologic suppression and improvement in clinical outcomes remain sustained in almost all patients even after treatment discontinuation.