The transplantation outcome depends largely on the prevention of hepatitis B recurrence. The spontaneous risk of HBV reinfection exceeds 75%, but major advances in prophylaxis during the last 15 years have led to the control of post-transplant hepatitis B reinfection in more than 90% of HBV transplants. Treatment with hepatitis B immune globulins (HBIG) plays a major role in prophylaxis, either as monotherapy in non-replicating patients or in combination with antiviral drugs in replicating subjects. Although no standardized therapeutic protocols have been defined, at present the prevailing approach is to use high-dose intravenous HBIG in the immediate perioperative period (first week, induction phase) and to administer over the long term monthly fixed or on-demand doses of intravenous or intramuscular HBIG (maintenance therapy), in association with antiviral(s). Results have been excellent, yet different strategies of long-term prophylaxis have been proposed in order to simplify therapy and reduce costs. Long-term prophylaxis with antiviral(s) and low-dose intramuscular HBIG seems to be the most promising option; in stable patients, the combination with antiviral agents reduces the need of HBIG, in particular when using on-demand administration protocols and intramuscular HBIG has proven as effective and safe as intravenous preparations during the maintenance phase.