Swine have become the preferred preclinical large animal model for transplantation research and potential xenograft donors for clinical transplantation due to their anatomical and physiological similarities to human. Compatibility of the swine MHC, or the swine leukocyte antigen (SLA), is among the most important immunological determinants in the setting of allo- and xeno-transplantation. In this webinar, we will review the current knowledge of the SLA system and its allele polymorphism and haplotype diversity characterized to date. We will also examine the importance of the SLA genes and proteins for the use of pigs as a routine large animal transplant model and a potential source of xenogeneic organs for human transplantation.