Staphylococcal infections remain an important cause of morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) present a particular problem because of the costs of treatment and containing outbreaks. The role of nasal carriage of staphylococci in the epidemiology of staphylococcal infection has been recognized for over 30 years. Until recently, eradication of nasal carriage of S. aureus has proved difficult, with a variety of topical and systemic agents yielding poor results with either little discernible effect on nasal carriage or rapid recolonization. Mupirocin is a novel topical antibiotic with excellent antibacterial activity against staphylococci, including MRSA. Intranasal administration of calcium mupirocin has achieved excellent results in the eradication of nasal carriage of S. aureus and producing an associated reduction in S. aureus infection in a variety of clinical settings, including MRSA outbreaks, neonatal nurseries, haemodialysis, cardiothoracic surgery and familial staphylococcal infections. This article reviews the efficacy and safety of intranasal mupirocin in the prevention of staphylococcal infections.