Post-transplant hepatitis B virus (HBV) recurrence prophylaxis is a sine qua non of liver transplantation for HBV-related liver disease because of high rate and aggressive course of HBV recurrence. Hepatitis B immune globulin (HBIG) is a polyclonal immune globulin solution obtained from plasma, donated by individuals with high titres of anti-HBs (hepatitis B antibody). Although it was being used for postexposure prophylaxis against HBV since 1974, its use in post-transplant prophylaxis of HBV infection was not until 1987. Long-term prophylaxis with HBIG alone had been the standard treatment in post-transplant HBV prophylaxis until the introduction of lamivudine. Combining HBIG with oral nucleotide/nucleoside analogues in post-transplant prophylaxis of recurrent HBV resulted in lower recurrence rates of infection. However, high cost and emergence of immune escape mutations are still the problems to be solved regarding HBIG therapy in post-transplant prophylaxis of HBV recurrence.