A long series of studies on mice has shown that mate choice decisions can be made on the basis of individual genotype at the major histocompatibility complex (MHC), which accords well with the importance of immunocompetence in some theories of sexual selection. Recent work on other vertebrate species, including humans, indicates that MHC-based mate choice is not restricted to the genus Mus. However, its importance may vary among species as a result of differences in social and mating system structure, and perhaps genome structure. There appears to be a general preference expressed for MHC-dissimilar mates, and such MHC-disassortative mating may be involved in maintaining MHC and/or genome-wide diversity in natural populations. The strength and direction of MHC-based mating preference can vary, and may be modulated by factors such as genetic background, sex, and early life experience.