Staphylococcus aureus is a ubiquitous bacterial species that causes serious disease in certain settings. S. aureus disease is difficult to treat, and antibiotic-resistant strains have become common. A vaccine to protect against infection would therefore be beneficial. However, the virulence of S. aureus is determined by a number of different factors, which makes design of a widely effective vaccine difficult. Here, various bacterial virulence factors and attempts to develop vaccines based on these factors are briefly reviewed. In particular, the success of a Phase 3 clinical study of a vaccine directed at capsular polysaccharides types 5 and 8 is discussed. (c) 2005 Elsevier Ltd. All rights reserved.