Topical antimicrobials may complement traditional infection control measures and hasten the control of an outbreak. When a suitable nonabsorbable antimicrobial regimen can be found, its use during outbreaks caused by Enterobacteriaceae colonizing the digestive tract appears especially attractive, whether the infection occurs via primary endogenous colonization or exogenous colonization. In the latter circumstance, however, topical antimicrobials are not a substitute for isolation precautions and careful handwashing, which remain insufficiently adhered to in ICUs. Topical antimicrobials should be used as part of a global strategy in which isolation precautions remain of primary importance. It is likely, but unproven by well-designed studies, that nasal decontamination of patient carriers during outbreaks due to methicillin-resistant Staphylococcus aureus can be useful to control the outbreak. In this instance, however, skin and wound disinfection appears as an essential complementary measure, and careful attention should be given to extranasal sites of colonization with MRSA, where resistance to the topical agent can emerge. Whatever the circumstances and setting, prolonged use of topical antimicrobials during protracted outbreaks is less effective and carries a major risk of resistance to the topical agent(s) used against the outbreak strains. In such circumstances, careful microbiologic monitoring of colonization is mandatory.