Infections associated with indwelling medical devices are frequently caused by Staphylococcus aureus or S. epidermidis. Bacteria can attach both to unconditioned biomaterial surfaces and to devices   that have been conditioned with host plasma proteins. Surface proteins can be involved in both scenarios. For example clumping factor and fibronectin binding proteins can promote attachment to fibrinogen and fibronectin, respectively. Until recently the accumulation phase was thought to require elaboration of polysaccharide called intercellular adhesin (ICA) or polysaccharide intercellular adhesin (PIA).  However this is often not the case and some clinical strains isolated from device-related infections lack the ica genes. Here the biofilm matrix develops from homophilic interactions between surface proteins, for example the  accumulation associated protein Aap of S. epidermidis  and fibronectin binding proteins by  some MRSA lineages. The mechanistic basis of homophilic interactions has been investigated by genetic, biochemical and biophysical approaches, including very recently by atomic force microscopy. If interaction sites on surface proteins can be identified it might be  possible to discover small molecules that block biofilm accumulation and have potential in novel future therapies.