The human leukocyte antigen (HLA) region on chromosome 6p21.3 is the most polymorphic in the human genome. It encodes hundreds of genes, of which the class I and class II HLA alleles play a central role in the generation of an immune response, but at the same time represent a barrier to marrow and organ transplantation. There is overwhelming evidence that optimal HLA matching will allow for safer marrow transplants, however with more than 1,200 allelic variants, the need to accurately identify the precise alleles is a technically demanding challenge. Methods currently in use for HLA typing include microcytotoxity assay, sequence-specific oligonucleotide (SSO) probe, sequence-specific primer (SSP) amplification, and sequence-based typing (SBT). Ambiguous results may still arise, even with the best molecular typing methods but this problem can be resolved by using a combination of methods. It is clear that a HLA typing laboratory will have to provide allele level resolution of HLA data using the most appropriate means available and this will have the greatest impact in terms of offering the best matched donor for the benefit of patients.