Since the discovery of the HLA system, over 40 years ago, we now have an understanding of the role of HLA molecules in the adaptive immune response, as well as in the alloimmune response experienced when foreign HLA is introduced into an individual via transplant, transfusion or pregnancy. Retrospective studies in the 1970s and 1980s illustrated the importance of matching for HLA antigens in transplantation and platelet transfusion. The huge degree of polymorphism in the system has driven the development of sensitive HLA typing and HLA antibody screening methods in H & I laboratories in order to improve transplant and transfusion outcomes.