Staphylococcus aureus is a versatile pathogen associated with diverse clinical presentations. Only recently have the genetic factors underlying the virulence of this bacterial species become understood in a significant way. Methicillin-resistant S. aureus (MRSA) strains have been extremely important as nosocomial pathogens in health care facilities for more than three decades. Additionally, infections resulting from community-associated MRSA strains have emerged in the last decade and become a public health problem of global proportions. This changing epidemiology has spurred renewed interest in translating knowledge of the molecular determinants of virulence into rational prevention and control strategies. Four case histories are provided (three involving MRSA and one involving a methicillin-sensitive strain of S. aureus) that highlight the diversity of clinical presentations and relative virulence of S. aureus infections in humans. The molecular characterization of clonality and virulence gene profile is compared among the four cases. Significant genetic diversity exists among MRSA and sensitive strains of S. aureus. It is obvious that various combinations of virulence factors contribute to disease manifestations of infected patients.