Abstract In areas where hepatitis B virus (HBV) is endemic, the increased use of cytotoxic or immunosuppressive therapy has resulted in an increased incidence of liver-related morbidity and mortality due to HBV reactivation in patients infected with the virus. As the hepatitis is preceded by HBV virological reactivation, administration of effective antiviral therapy to HBV (anti-HBV) such as lamivudine preemptively before or at the initiation of cytotoxic therapy and to cover the entire period of immunsuppression, has greatly reduced the risk of liver-related morbidity and mortality due to HBV reactivation. However, such an early ‘preemptive’ approach runs the risk of over-treating patients who might not be suffering from HBV reactivation with nucleoside analog. In addition, the duration of therapy with nucleoside analog, such as lamivudine, would be longer with this approach. Taken together, such an indiscriminant preemptive approach could result in an increased risk of developing HBV viral resistance. Indeed, severe liver damage due to the development of mutations in the polymerase gene related to lamivudine, namely at M204V and at L180M, has been reported in hepatitis B surface antigen (HBsAg) positive recipients of allogeneic bone marrow transplantation and who were treated with preemptive lamivudine. In order to further optimize the management of postchemotherapy HBV reactivation, more studies aiming to identify risk factors for HBV reactivation after chemotherapy should be undertaken.