The control of methicillin-resistant Staphylococcus aureus (MRSA) is still an unresolved issue in numerous healthcare institutions worldwide. Guidelines for the control of MRSA in hospitals focus on measures to control cross-transmission and prevent colonization, but rarely specifically mention the control of antimicrobial use. We reviewed the different types of evidence for a causal relationship between MRSA and antimicrobial use by classifying them in four categories: consistent associations, dose-effect relationships, concomitant variations, and arguments to support a plausible biological model to explain this relationship. Although the relative participation of cross-transmission and antimicrobial selection pressure in the level of MRSA observed in a healthcare setting remains to be determined, we found lines of evidence to support the existence of a relationship between MRSA and antimicrobial use in each of the four categories. This review points out the relative lack of studies specifically designed to investigate this aspect of MRSA epidemiology and the need to implement such studies quickly. In the meantime, the results presented here should encourage the implementation of antimicrobial-use improvement programs in hospitals in addition to existing infection control measures, which are still a priority in countries with high MRSA prevalence.