The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in animals such as horses, pet animals and productive livestock has raised questions of a probable human origin and in more general of host specificity of S. aureus. Particular clonal lineages are obviously specific for humans (e.g. ST15, ST25, ST45) and other for ruminants (e.g. ST151). MRSA associated with veterinary nosocomial infections (e.g. ST8 and ST254 in horses, ST22 in small animals) very likely have their origin in health care facilities. MRSA ST398 which became first known from widespread colonization in industrially raised pigs seems to have a limited host specificity and is able to colonize and to cause infections in various hosts. Mechanisms of host adaptation and their genomic background are poorly understood so far.