The increasing incidence of a variety of infections due to Staphylococcus aureus--and, especially, the expanding role of community-associated methicillin-resistant S. aureus (MRSA)--has led to emphasis on the need for safe and effective agents to treat both systemic and localized staphylococcal infections. Unlike most previously noted strains of health care-associated MRSA, community-acquired MRSA isolates are often susceptible to several non- beta -lactam drug classes, although they are usually not susceptible to macrolides. Several newer antimicrobial agents and a few older agents are available for treatment of systemic staphylococcal infections, but use may be limited by the relatively high cost of these agents or the need for parenteral administration. Inexpensive oral agents for treatment of localized, community-acquired MRSA infection include clindamycin, trimethoprim-sulfamethoxazole, and newer tetracyclines. Clindamycin has been used successfully to treat pneumonia and soft-tissue and musculoskeletal infections due to MRSA in adults and children. However, concern over the possibility of emergence of clindamycin resistance during therapy has discouraged some clinicians from prescribing that agent. Simple laboratory testing (e.g., the erythromycin-clindamycin "D-zone" test) can separate strains that have the genetic potential (i.e., the presence of erm genes) to become resistant during therapy from strains that are fully susceptible to clindamycin.