Staphylococcus aureus is a fastidious pathogen of global concern. S. aureus can not only cause a wide range of serious infections, but can also colonize healthy individuals. Nosocomial- associated S. aureus infection is a major concern for healthcare facilities. Recent increases in antibiotic resistance and community-acquired infection highlight the need for improved understanding for prevention and treatment of this pathogen. This minireview addresses the current state of S. aureus prevalence, correlates of immunity, and vaccine development.