The emergence and clonal expansion of strains of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) have created new challenges with their entrance to hospitals. The increased virulence of CA-MRSA in concert with the depressed immunity of inpatients may cause added morbidity and mortality expected from healthcare-associated infections. Questions about changing prophylactic and empirical therapy as well as the use of intravenous immunoglobulin for life-threatening infections are addressed.