The HLA match maker is an interesting computer algorithm assessing the degree of HLA matching or mismatching according to the number of antigenic epitopes shared or not between donor and recipient. These antigenic epitopes are referred to as eplets, which represent the conformational epitopes formed by the polymorphic aminoacid residues able to elicit an immune alloresponse, more specifically an antibody response. The number of mismatched HLA eplets has been shown to associate with transplant outcomes and anti-HLA antibody production in kidney transplant patients. Furthermore, the HLA matching based on this algorithm has proven to increase the chances to find suitable donors in highly sensitised patients through the principle of “acceptable vs taboo mismatches”. Thus, an individual can be mismatched according to the traditional HLA matching model, but the eplet level the patient might not have an unacceptable mismatch, because donor and recipient might share the same eplets between their respective HLA molecules, or because the dose of eplets given by the donor HLA molecules is lower than in other donor-recipient HLA allele combinations. Therefore, HLA matchmaker appears to be the most reliably and intelligent method up to date to relate HLA matching/mismatching with transplant outcomes and to quantify the degree of mismatch by counting the number of mismatched epitopes or eplets, which can be regarded as the epitope or eplet load. However, the HLA matchmaker can only be applied if four-digit split HLA typing resolution has been achieved or inferred through a four-digit convertor provided by the HLA matchmaker founders.