In the past, reinfection of the graft by hepatitis B virus (HBV) after liver transplantation for HBV-related liver disease was often followed by severe liver damage and reduced survival. The long-term administration of hepatitis B immunoglobulin (HBIG) dramatically reduced this risk. However, this procedure was ineffective in most patients with active viral replication pre-transplant. The use of lamivudine in the pre-transplant setting partially solved this problem. The emergence of resistant mutants to lamivudine was also solved by the addition of adefovir. At present, combination therapy by oral antivirals pre-transplant and HBIG plus the same drugs post-transplant achieves nearly 100% of protection against graft reinfection. In a recent study, a new intravenous HBIG, Niuliva has shown high efficacy in achieving protective anti-HBs levels after liver transplantation for HBV-related liver diseases, as well as a good safety profile. Using combination therapies, the doses of HBIG can be reduced or even stopped after several weeks or months post-transplant, continuing with oral antivirals alone. The recently introduced antivirals achieve a very high antiviral potency and low risk of resistance. This may further increase the efficacy in preventing graft reinfection in the post-liver transplantation setting.