Fifty years ago methicillin-resistant Staphylococcus aureus (MRSA) first revealed themselves to the medical community, having been described in a landmark article published in the British Medical Journal. Among other things, their discovery set off a major response from the scientific and medical professions to control or even eliminate them as major human pathogens. Despite these efforts, however, MRSA have spread throughout the world and a half century after they burst upon the scene they continue to pose major challenges to research scientists and clinicians alike. In a very real sense, this year marks the 'birthday' of a remarkably successful pathogen. The major reasons for the ability of MRSA to prosper and cause disease in settings inimical to its survival form the basis of this article.