Decolonization may be defined as treatment to eradicate Staphylococcus aureus or methicillin-resistant S aureus (MRSA) carriage. Potential benefits of decolonization include decreased risk of subsequent staphylococcal infection and prevention of staphylococcal transmission to reduce endemic rates of infection or manage outbreaks. This article reviews available data regarding various proposed treatment regimens for eradicating staphylococcal carriage and the effectiveness of decolonization for infection prevention and as an infection control measure.