The Liver allograft has been considered a privileged organ resistant to insults from humoral and cellular alloimmunity. However, liver allograft rejection happens, especially in the presence of strong donor-specific antibodies (DSAs) to class II human leucocyte antigens (HLA). This chapter summarizes commonly used histocompatibility tests before and after liver transplantation. The purpose is to provide an overview of HLA service for liver transplant physicians and surgeons, from the perspective of HLA experts. Two cases were presented to illustrate the assessment of strong DSAs before and after liver transplantation, either liver-alone or combined with another organ. These cases highlight the importance of collaboration between the HLA lab and clinicians in managing complicated patients.