Antimicrobial drugs encourage the overgrowth of organisms resistant to the agents used. Acquisition and subsequent overgrowth of methicillin-resistant Staphylococcus aureus (MRSA) are particularly associated with beta-lactam antibiotics and quinolones. These drugs allow rapid proliferation of an organism that might have been merely colonizing the skin, leading to clinical infection, treatment difficulties and potential transmission to others. In addition, there is increasing evidence that inappropriate antibiotics not only encourage overgrowth with MRSA but may also enhance pathogenicity. Such virulence is not necessarily due to simple expansion of MRSA across skin and mucosal surfaces; there appear to be molecular changes that facilitate mechanisms such as quorum sensing, adhesion, phage mobilization, exotoxin production, intracellular persistence and biofilm formation, all of which contribute towards more severe infection. This review examines the association between MRSA and certain classes of antibiotics and explores the molecular mechanisms underlying a perceived increase in virulence following inappropriate therapy. It is possible that empirical prescribing has a significant impact on the management of MRSA infections and ultimately patient outcome. It is time to challenge the prescribers' right to prescribe what they like, when they like, for patients at risk of MRSA.