The major histocompatibility complex (MHC) on chromosome 6 is one of the most intensively studied regions of the human genome and has many features which make it unique. It is the source of much research interest because of its role in autoimmune and infectious disease susceptibility, and of diagnostic interest because of its role in transplantation and rejection. It is the most gene-dense and SNP-rich region of the genome, with large number of complex haplotypes and other features which must be taken into account when analysing the MHC in the laboratory. This article provides a brief overview of the MHC highlighting some of the issues that must be considered when developing new methods and assays.