One of the major factors that have contributed to improving the outcomes of Stem Cell Transplantation is progress made in the field of human leucocyte antigen(s) (HLA). This is evident not only in developing techniques for rapid and accurate tissue typing, but also in the greatly improved understanding of the HLA system and the impact of HLA matching on transplant complications. It is now accepted that high-resolution HLA matching for transplant recipients and unrelated donors is associated with the best clinical outcomes. The most important HLA determinants are the six ‘classical’ polymorphic HLA loci: HLA-A, -B, -C, -DRB1,-DQB1, -DPB1. For several years, based on the outcome of numerous studies, a 10/10 matched donor (HLA-A, -B, -C, -DRB1, -DQB1) was considered the ideal. The impact of HLA-DPB1 has been less clear, in view of reduced likelihood of patient/donor matching for this locus. More recently, several large studies have questioned the importance of HLA-DQB1 matching on outcome. Based on the findings of recent studies, the current gold standard unrelated donor is believed to be one matched for 8/8 alleles at high resolution i.e. matched for HLA-A, -B, -C, -DRB1, however, in certain circumstances, mismatches may be tolerated and/or permissive.