With the rising importance of nosocomial infections in equine hospitals, increased efforts with regard to biosecurity and infection control are necessary. This even more since nosocomial infections are often associated with multi-drug resistant pathogens. Consequently, the implementation of targeted prevention programs is essential. Since nosocomial infections are usually multifactorial events, realization of only a single measure is rarely effective to overcome nosocomial spread in clinical practice. Equine patients may be colonized at admission with multi-drug resistant pathogens such as methicillin resistant Staphylococcus aureus (MRSA) and/or extended spectrum beta lactamase-producing (ESBL-) Enterobacteriaceae. Regardless of their individual resistance properties, these bacteria are common and usually unnoticed colonizers of either the nasopharynx or the intestinal tract. Also viral diseases caused by equine herpesvirus 1 (EHV-1) and EHV-4 may reach a clinic by patients which are latently infected or in the incubation period. To prevent nosocomal outbreaks, achieve an interruption in the infection chain and to eradicate infectious agents from the hospital environment, a professional hospital management is necessary. This should be adapted to both the wide range of pathogens causing nosocomial infections and the individual needs of equine patients. Amongst others, this approach includes a risk classification of equine patients at admission and information/enlightenment of the animal owners at discharge. An efficient management of inpatients, a targeted hygiene management and clear responsibilities with respect to biosecurity together with a surveillance of nosocomial infections form the cornerstone of infection control in equine hospitals.