There are numerous resistant microorganisms but meticillin-resistant Staphylococcus aureus (MRSA) is probably the most notorious. MRSA is a resistant variation of the common bacterium, Staphylococcus aureus, that has developed the ability to survive treatment with a number of beta-lactam antibiotics, including meticillin. The focus of this article is a narrative literature review concerning the challenge that MRSA presents to nurses and other healthcare workers. A historical overview of antimicrobial resistance and the origins of MRSA are given, together with the factors involved in the persistence of antimicrobial resistance. The relevant microbiology, pathogenesis and epidemiology of MRSA will be discussed to provide a detailed rationale for the contemporary management of this persistent, resistant organism.