Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infection has become epidemic. Skin and soft-tissue infections (SSTIs) are the most frequent forms of the disease. Obtainment of culture specimens is important for documentation of the presence of MRSA and for susceptibility testing to guide therapy. Purulent lesions should be drained whenever possible. In areas where community-acquired MRSA isolates are prevalent, uncomplicated SSTI in healthy individuals may be treated empirically with clindamycin, trimethoprim-sulfamethoxazole, or long-acting tetracyclines, although specific data supporting the efficacy of these treatments are lacking. In healthy patients with small purulent lesions, drainage alone may be sufficient. In patients with complicated SSTI requiring hospitalization or intravenous therapy, vancomycin is the drug of choice because of the low cost, efficacy, and safety. Linezolid, daptomycin, and tigecycline are also effective, although published studies on the last 2 agents for the treatment of SSTI due to MRSA are more limited. Dalbavancin, telavancin, and ceftobiprole are investigational agents that may expand our therapeutic options for the treatment of SSTI caused by MRSA.