Reactivation of hepatitis B virus (HBV) is a well-recognized complication of chemo/immunosuppressive therapy in individuals who are HBV surface antigen-positive inactive carriers and in individuals with chronic HBV infection. Although it is well established that chemo/immunosuppressive therapy enhances HBV replication with a resultant increase in the viral load and disease activation, the role of prophylactic lamivudine therapy to prevent chemo/immunosuppressive therapy-induced HBV activation in HBV-positive individuals who are to receive chemo/immunosuppressive therapy remains controversial. The aims of the present article are: (i) to determine the effect of lamivudine prophylaxis in HBV carriers with haemato-oncological malignancies who require chemotherapy; (ii) to define the duration and safety of lamivudine in such individuals; and (iii) to identify the effect of lamivudine prophylaxis on the outcome of chemotherapy administered for the primary disease. The data currently available suggest that lamivudine prophylaxis prevents chemotherapy-induced HBV reactivation in HBV carriers with haemato-oncological malignancies who receive chemotherapy. Lamivudine is safe and tolerable in such individuals. The duration of lamivudine prophylaxis is not yet known; however, it would appear prudent to begin lamivudine at the time of the initiation of the chemotherapy and to continue it throughout the period of chemotherapy administration and for at least 1 and possibly 2 years following the discontinuation of the chemotherapy. Finally, the prophylactic use of lamivudine in inactive HBV carriers with haemato-oncological malignancy prevents interruptions in their treatment for primary disease as a result of HBV reactivation.