Methicillin-resistant Staphylococcus aureus (MRSA) infections have become a major pathogen in community and health care facilities. Because of the high incidence of infections in both settings, there is increased attention to understanding the value of interventions to prevent MRSA infection. Methicillin-resistant Staphylococcus aureus infection may be fueled or spread by MRSA colonization on the human body. Methicillin-resistant Staphylococcus aureus colonization may be more common than previously reported given that some patients are colonized only in nonnasal sites. Methicillin-resistant Staphylococcus aureus transmission may also be facilitated by spread from contaminated objects, many of which can easily be contaminated with MRSA. This article reviews current data on MRSA prevention in the community and health care facilities. Although currently prevention data are very limited, the role of body decolonization with topical antimicrobials and systemic antibiotics is discussed as is the environmental decontamination. Finally, the value of hospital-based interventions such as contact isolation, MRSA screening, and decolonization of hospitalized patients is discussed.