Infections involving the skin and soft tissue are common and range from superficial, localized and sometimes self-limiting infections to deep, rapidly spreading and potentially life-threatening infections. Skin infections caused by Staphylococcus aureus include primary pyodermas, while those involving the soft tissues include cellulitis and pyomyositis. Surgical site infections and infections in intravenous drug users are also commonly caused by S. aureus. The severity of the infection determines the choice of treatment. There are few studies that have critically appraised the use of antibiotics in skin and soft tissue infections, and most guidelines are based on expert opinion. The beta-lactam group of antibiotics are the mainstay of treatment for methicillin-susceptible S. aureus infections. For methicillin-resistant S. aureus (MRSA) infections, both with community-acquired and hospital-acquired strains--which are becoming an increasing problem--the antibiotic choice is determined by local susceptibility patterns. Macrolides, clindamycin and cotrimoxazole are options for community-acquired MRSA, while vancomycin is reserved for treatment of infections caused by multiresistant MRSA strains and for patients with suspected endocarditis or severe sepsis. Although a number of the newer antibiotics such as linezolid and quinopristin/dalfopristin have been shown to have good activity against MRSA, these agents should only be used with specialist advice.