The acquisition of Staphylococcus aureus by the newborn in the early neonatal period is common. Most such acquisitions are not followed by infection, although the potential for serious infection increases in the intensive care unit setting. Attack rates for infection are quite variable, but outbreaks have occurred on many occasions. Although some bacterial virulence factors, such as exfoliative toxins, are associated with outbreaks, most epidemic strains do not have well-defined virulence factors that can be incriminated. There are many possible control measures, but the implementation of these are balanced by the existing circumstances and perceived cost. As methicillin-resistant S. aureus (MRSA) becomes endemic in hospital settings, these bacteria are becoming much more common in nursery outbreaks. Over time, antibiotic selection and enhanced disease causation will lead to the evolution of hypervirulent MRSA clones. The latter will become an increasing problem unless effectively controlled.