With its wealth of mobile genetic elements, Staphylococcus aureus has undergone rapid evolutionary change during the antibiotic era.  Much of this evolution has been driven by antibiotic use and the many successful clones of MRSA attest to this.  Fortunately most of these clones are not very virulent as the multiple resistance determinants carry a fitness cost.  USA 300 has, however, demonstrated a different evolutionary approach with less resistance but fitness genes such as ACME and PVL making it very successful, firstly in the community and now in hospitals. While hospital MRSA is traditionally seen as primarily an infection control problem, antibiotic stewardship has a major role to play in its control.  Use of cephalosporins in particular, and quinolones and macrolides where strains are resistant, are major drivers of MRSA in our hospitals and reducing their use is a very effective  MRSA control measure in addition to hand hygiene, admission screening, isolation or cohorting and body decontamination.  Mupirocin and chlorhexidine are the most commonly used agents for such decontamination although there are many possible alternatives. Vancomycin has been the mainstay of treatment for severe MRSA infections but it is toxic and we are still learning optimum dosing schedules, even after 50 years of use!  Increasing use has led to increasing resistance by various mechanisms notably MIC creep and plasmid mediated high level resistance (vanA).  Both old agents such as doxycycline and cotrimoxazole and newer agents such as linezolid and daptomycin offer alternatives.  5^th generation cephalosporins such as ceftaroline also offer useful activity.