Methicillin-resistant Staphylococcus aureus (MRSA) was first described in 1961 (21) in England. Since then, MRSA has been found all over the world, and has become one of the major nosocomial agents in the hos pital. This review is intended to summarize the recent achievements on the molecular evolution of methicillin resistance. I shall try to present a rather simple under standingon this subject, describing step-wise genetic changes to achieve full expression of methicillin resis tanceby MRSA; the first step is the acquisition of mec (standing for methicillin resistance)-region DNA by a methicillin-susceptible S. aureus (MSSA) on its chro mosome, the second step is the inactivation of the mecI gene (encoding a mecA gene repressor), and finally, the third step is an alteration of chromosomal locus or loci to acquire high methicillin resistance. I shall review recent important works according to this scheme of three-step genetic evolution of MRSA.