The ability of animals to resist infections with parasites is genetically determined and therefore variable between individuals or breeds of a given host species. Such variation may involve innate (non-immunological) and acquired (immunologically mediated) resistance mechanisms, and is determined by both major histocompatibility complex (MHC)-linked and non-MHC genes. Resistance is inherited as a dominant trait, with heritability often exceeding 0.3. Genetic variation can be exploited to improve the capacity of domestic animals to resist parasitic infection. Methods to achieve this exploitation are discussed in relation to gastrointestinal nematode infections in sheep.