Methicillin-resistant Staphylococcus aureus (MRSA) has emerged since the 1960s, spread globally, and become a leading cause of bacterial infections in both healthcare and community settings. MRSA is resistant to most β-lactam antibiotics, including methicillin, and has various clones due to the independent acquisition of the staphylococcal cassette chromosome mec (SCCmec). MRSA is often resistant to multiple other antibiotic classes. S. aureus is a Gram-positive, nonmotile, coagulase-positive coccus found in the human nasal microbiota of 20–40% of the population. When the cutaneous and mucosal barriers are disrupted, S. aureus can gain access to underlying tissues or the bloodstream and cause infection. Individuals with invasive medical devices or compromised immune systems are particularly vulnerable to S. aureus infection. MRSA was first described in England in 1961, soon after methicillin was introduced into clinical practice. Methicillin was initially widely used, but due to its toxicity, it is no longer marketed for human use and has largely been replaced by similar, more-stable penicillins. However, the term methicillin-resistant S. aureus continues to be used. In the decade following its initial description, MRSA was responsible for hospital outbreaks (health-care-associated MRSA (HA-MRSA)) in many parts of the world. A substantial change in MRSA epidemiology was observed when it was detected in individuals without previous health-care contact (referred to as community-associated MRSA (CA-MRSA)), notably among indigenous populations in Australia in the 1980s and otherwise healthy persons, including children, in the United States in the 1990s. Since the mid-2000s, it has also been associated with livestock exposure (livestock-associated MRSA (LA-MRSA)). MRSA is often also resistant to multiple other antibiotic classes. Indeed, S. aureus has the remarkable ability to acquire resistance to any antibiotic, which has major implications for current as well as future treatment options for this pathogen. Individuals with MRSA colonization or carriage have an increased risk of subsequent infection and are an important source of person-to-person transmission. Health-care facilities host persons who are predisposed to infection and are environments with high antibiotic selection pressure and frequent contact between individuals. These conditions have facilitated the epidemic spread of MRSA in hospitals; MRSA is now endemic in many health-care facilities throughout the world and, as a consequence, it has become a major focus for infection control efforts globally. This Primer reviews the epidemiology, pathophysiology, diagnosis, prevention, management and clinical effect of MRSA, focusing on HA-MRSA, and discusses future research priorities. In some aspects of the epidemiology and pathophysiology, where methicillin resistance does not substantially affect theMethicillin-resistant Staphylococcus aureus (MRSA) has emerged since the 1960s, spread globally, and become a leading cause of bacterial infections in both healthcare and community settings. MRSA is resistant to most β-lactam antibiotics, including methicillin, and has various clones due to the independent acquisition of the staphylococcal cassette chromosome mec (SCCmec). MRSA is often resistant to multiple other antibiotic classes. S. aureus is a Gram-positive, nonmotile, coagulase-positive coccus found in the human nasal microbiota of 20–40% of the population. When the cutaneous and mucosal barriers are disrupted, S. aureus can gain access to underlying tissues or the bloodstream and cause infection. Individuals with invasive medical devices or compromised immune systems are particularly vulnerable to S. aureus infection. MRSA was first described in England in 1961, soon after methicillin was introduced into clinical practice. Methicillin was initially widely used, but due to its toxicity, it is no longer marketed for human use and has largely been replaced by similar, more-stable penicillins. However, the term methicillin-resistant S. aureus continues to be used. In the decade following its initial description, MRSA was responsible for hospital outbreaks (health-care-associated MRSA (HA-MRSA)) in many parts of the world. A substantial change in MRSA epidemiology was observed when it was detected in individuals without previous health-care contact (referred to as community-associated MRSA (CA-MRSA)), notably among indigenous populations in Australia in the 1980s and otherwise healthy persons, including children, in the United States in the 1990s. Since the mid-2000s, it has also been associated with livestock exposure (livestock-associated MRSA (LA-MRSA)). MRSA is often also resistant to multiple other antibiotic classes. Indeed, S. aureus has the remarkable ability to acquire resistance to any antibiotic, which has major implications for current as well as future treatment options for this pathogen. Individuals with MRSA colonization or carriage have an increased risk of subsequent infection and are an important source of person-to-person transmission. Health-care facilities host persons who are predisposed to infection and are environments with high antibiotic selection pressure and frequent contact between individuals. These conditions have facilitated the epidemic spread of MRSA in hospitals; MRSA is now endemic in many health-care facilities throughout the world and, as a consequence, it has become a major focus for infection control efforts globally. This Primer reviews the epidemiology, pathophysiology, diagnosis, prevention, management and clinical effect of MRSA, focusing on HA-MRSA, and discusses future research priorities. In some aspects of the epidemiology and pathophysiology, where methicillin resistance does not substantially affect the