The coagulase-negative staphylococci and, in particular, Staphylococcus epidermidis, have emerged as major nosocomial pathogens associated with infections of implanted medical devices. These organisms, which are among the most prevalent bacteria of the human skin and mucous membrane microflora, present unique problems in the diagnosis and treatment of infections involving biofilm formation on implanted biomaterials. Epidemiological data that address whether invasive S. epidermidis strains can be traced to commensal organisms or an endemic occurrence of distinct strains with enhanced virulence have important implications for the implementation of appropriate infection control measures. An extracellular polysaccharide adhesin represents a key virulence determinant in S. epidermidis and is required for biofilm formation. Production of this adhesin, which is encoded by the ica operon, is subject to phase variable regulation (ON OFF switching). Recent advances in understanding the molecular events controlling polysaccharide adhesin synthesis and the potential clinical implications of its phase variable regulation are outlined. Further research in this area may contribute to the development of novel strategies for therapeutic intervention. Finally, in addition to antibiotic prophylaxis, preventive strategies to control S. epidermidis medical device-related infections are focusing on the development of improved biomaterials and physical electrical barriers to impede bacterial colonisation.