In the field of immunohematology, blood group genotyping has become a very common approach for routine purpose to complement the gold standard serological studies, and to further guarantee the safety of patients. It has more recently explored the major advances in the available technologies for molecular analysis, including next‐generation sequencing (NGS). NGS, known as second‐generation technologies in its current format, has revolutionized the field of molecular genetics for the past decade. For the very recent years, a few pilot studies using various commercial platforms have paved the way towards blood group genotyping by NGS in both transfusion and obstetric medicine. Advantages and limitations have been reported, and future trends for improvements have been clearly identified. Third‐generation sequencing, which is interestingly characterized by the production of long reads that have been shown to cover up to several dozen kilobases, has also become available in the meantime. This novel technology shows great promises for clinical applications in the very next future, most importantly by resolving the challenging issue of characterizing gene conversion events occurring in genes of the Rh and MNS blood group systems. By considering recent and future advances in these technologies and their related bioinformatics resources, it is tempting to suggest that a routine, NGS‐based strategy will be soon available for blood group genotyping with high accuracy at a low cost. Clinical utility and clinical applications of this technology remain to be evaluated.
