The major histocompatibility complex (MHC), a gene-dense genomic region present in all jawed vertebrates, are the most polymorphic genes in vertebrate genomes. They play key roles in immune function via immune-recognition and -surveillance and host-parasite interaction. MHC genes are increasingly common for studies of immunology, genetics, and evolution as well as conservation biology. The organization and evolution of MHC genes vary considerably among vertebrate lineages. MHC genes have been well characterized in mammals, birds, amphibians and fishes, but little is known about their organization in reptiles, despite the fact that reptiles occupy an important phylogenetic position for understanding the evolutionary history of vertebrates MHC genes. Here, we review the molecular structure, the maintaining mechanisms of MHC polymorphism and their function in reptiles. We also review the field and focus on the successful applications of MHC-typing for population genetic studies and conservation management in reptiles. We conclude this review by proposing several directions where future research is needed.