A review of the pathogenesis, clinical manifestations, diagnosis, and therapy of staphylococcal skin and skin structure infections begins with discussion of the staphylococcal carrier state. Patients carrying Staphylococcus aureus are particularly vulnerable to infection if their skin is broken by wounds or placement of intravenous lines or catheters. S. aureus begins the process of infection by binding tightly to fibronectin-coated surfaces and endothelial cells; bacterial invasion, however, depends on the innate pathogenicity of the bacterial strain and on the status of the host's defenses. The carrier state may be manifested by recurrent infections in the skin and skin structures. Infection may be spontaneous, associated with skin trauma and/or presence of a foreign body, or related to the presence of bacteria. For diagnosis, appropriate samples of purulent materials are needed for Gram stain and culture. Drainage is absolutely essential. Most staphylococci are now penicillinase-producing. Initial coverage with a cell-wall-active agent combined with an aminoglycoside is usually highly effective. If a methicillin-resistant organism is suspected, vancomycin should be used. Treatment of the carrier state may eliminate recurrent episodes of staphylococcal skin infection. Meticulous infection-control procedures are extremely important in the prevention of staphylococcal infection of the skin and skin structures.