Methicillin-resistant Staphylococcus aureus (MRSA) bacteria are a common cause of hospital- and community-acquired infections. Persons may have asymptomatic colonization with MRSA in the nares, axillae, perineum, or groin. Since MRSA colonization often precedes infection, and infection is associated with significant morbidity and mortality, there is great interest in preventing the transmission of MRSA and decolonizing persons who harbor these bacteria. We provide an evidence-based review of MRSA decolonization agents. Our search strategy included the databases of the Cochrane Central Register of Controlled Trials, MEDLINE (1962-May 2008), and EMBASE (1980-May 2008). To identify unpublished trials, abstract books from appropriate major scientific meetings were hand searched, manufacturers were contacted, and pharmacology references were researched for available commercial products, formulations, adverse events, and dosing. The most extensive research in MRSA decolonization has been conducted with mupirocin, which is applied to the anterior nares 2-3 times/day for 5 days. Increased use is correlated to resistance development; therefore, routine decolonization is not prudent unless MRSA colonization is confirmed in the nares or other site. Retapamulin is under investigation for use in nares decolonization. If total body decolonization is necessary, bathing or showering with an antiseptic agent such as chlorhexidine gluconate is recommended in combination with mupirocin applied to the nares to improve the likelihood of eradication. Oral antibiotics have been evaluated for use in decolonization of the skin and nares but should be considered only in conjunction with topical agents and when all other decolonization attempts and environmental controls have been exhausted. Homeopathic and investigational agents may also be effective. Although mupirocin is the standard of care for decolonization of MRSA, several agents demonstrate efficacy and many merit further investigation.