Publisher Summary This chapter discusses that bone marrow transplantation (BMT) is more sensitive to HLA difference than solid-organ transplantation. The success of transplantation depends upon the HLA match between donor and recipient. Various other minor histocompatibility antigens have been defined by studying alloreactive CDS T-cell responses in patients who have received HLA-identical bone marrow transplants. For those patients who need a bone marrow transplant and do not have an HLA compatible donor within the family, a search can be made for an unrelated donor, who is HLA matched. Graft-versus-host disease (GVHD) is caused by mature T cells in the transplanted bone marrow, which may even derive from the peripheral blood that contaminates all bone marrow aspirates. In bone marrow transplantation the immunological situation is different from that in solid organ transplantation. Here the recipient's immune system is deliberately destroyed by treatment with radiation and cytotoxic drugs, before transplantation with a source of pluripotent haematopoietic stem cells that will in time reconstitute the immune system. The dominant alloreactions that arise after bone marrow transplantation are caused by mature T cells in the transplanted bone marrow, which respond to the major and minor histocompatibility antigens expressed by the cells and tissues of the recipient.