Hospitals are faced with the increasingly rapid emergence and dissemination of antimicrobial-resistant microorganisms. US and European guidelines on the prevention of antimicrobial resistance in hospitals were, until recently, mainly directed at methicillin-resistant Staphylococcus aureus (MRSA). In 2004, the Dutch Working Party on Infection Prevention issued a guideline on the prevention of nosocomial transmission of highly resistant microorganisms (HRMO), in order to fulfill the growing need for additional guidance on the control of other pathogens with acquired resistance and the potential to spread within hospitals (such as glycopeptide-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, extendedspectrum beta-lactamase producing Enterobacteriaceae, and other (multi)drug-resistant gram-negatives). In addition to providing criteria for defining HRMO, the Dutch guideline provides recommendations on isolation of patients, active surveillance, and contact tracing. The guideline will enable the comparison of HRMO rates between hospitals, and may be used to evaluate the efficacy of programs to control antibiotic use and/or nosocomial transmission of resistant pathogens. The eventual success of nationwide implementation of this guideline remains to be established in the coming years.