Combination therapy with hepatitis B immunoglobulin (HBIG) plus nucleos(t)ide analogue have reduced the rate of hepatitis B virus (HBV) recurrence post-transplantation to less than 10% at long-term. HBV recurrence diagnosed after 3 years post-transplantation is extremely rare. Considering the cost and the constraints of HBV prophylaxis it was suggested to decrease the amount of HBIG given and possibly to discontinue HBIG administration. The additional debate was on the need to maintain or not any HBV prophylaxis at long-term or to maintain monoprophylaxis with one or two nucleos(t)ide analogues or to administer HBV vaccine: The supporters of this strategy argued that HBV recurrence can be easily controlled by administration of nucleos(t)ide analogues. However, it was shown that 50-80% of patients maintain HBV DNA in the liver, serum or peripheral mononuclear blood cells long-term after transplantation. In patients receiving monoprophylaxis with nucleos(t)ide analogues the risk of HBV reinfection increases with time due to HBV mutant strains. Vaccine protocols used to replace HBIG prophylaxis gave disappointing results. Combination protocols using low-doses of intramuscular HBIG plus nucleos(t)ide analogues have been associated with a low rate of HBV reinfection. In conclusion, long-term prophylaxis should be maintained in most patients except those with anti-HBs seroconversion.