Staphylococcus aureus, a major opportunistic pathogen responsible for a broad spectrum of infections, naturally inhabits the human nasal cavity in about 30% of the population. The unique adaptive potential displayed by S. aureus has made it one of the major causes of nosocomial infections today, emphasized by the rapid emergence of multiple antibiotic-resistant strains over the past few decades. The uncanny ability to adapt to harsh environments is essential for staphylococcal persistence in infections or as a commensal, and a growing body of evidence has revealed critical roles in this process for cellular structural dynamics, and population heterogeneity. These two exciting areas of research are now being explored to identify new molecular mechanisms governing these adaptational strategies.