Despite impressive progress in fish farming during the last years, the impact of fish diseases is still an important problem in aquaculture. Current methods to control diseases consist, among others, of medication or eradication of diseased animals in combination with disinfection of facilities. Another alternative approach is to prevent diseases by improving the immune capacity of fish by vaccination or genetic selection. It is known from studies in mammals, that a limited number of major genes, including the major histocompatibility complex (MHC), is involved in the regulation of the immune response. The existence of a classic MHC in fish is still a matter of debate. Recently, the dogma of the MHC being a single chromosomal region was challenged by investigations into the segregation of MHC genes in fish and other vertebrates. The observed absence of linkage between class I and class II major histocompatibility genes in fish would allow for an independent segregation of immunological traits associated with cytotoxic responses to virus infection (class I) or humoral responses to bacteria (class II). This could be an explanation why in challenge experiments the resistance to one disease is not necessarily correlated with resistance to another disease.