Most of the genes in the major histocompatibility complex region express extremely high intrapopulational polymorphism. Such polymorphism in virtually all vertebrates can hardly be interpreted as an incidental phenomenon, and dozens of theories have attempted to elucidate the evolutionary pressures that have shaped it. First, the polymorphism is maintained by heterozygote advantage. As HLA gene expression is co-dominant, HLA heterozygotes express absolutely more types of functional HLA proteins than homozygotes and are thus able to present a broader spectrum of peptides. Second, the HLA polymorphism is a result of frequency-dependent selection in an evolutionary arm race between pathogens and the vertebrate immune system. According to this scenario, pathogens rapidly evolve the ability to escape recognition of most common host genotypes, for example by mutation that eliminates all peptides which affinities to common variants of the host HLA genes. Third, the maintenance of HLA polymorphism under variable selection over time due to a varying degree of pathogen presence. It shows that temporal variation inresistance itself can maintain polymorphysm even without co-dominant-based heterozygote advantage. Finally, the HLA polymorphism is maintained by sexual selection. Individuals of one or both sexes prefer partners possessing a relatively dissimilar partners increases offspring heterozygosity at the HLA and therefore can potentially increase pathogen resistance in resulting progeny.