The intravascular manifestation of Staphylococcus aureus infection is often associated with a severe, and sometimes catastrophic disease. Many host factors contribute to endothelial tropism of S.aureus including subendothelial matrix proteins, endothelial cell receptors, and platelets that are engaged together with S. aureus cell wall adhesins such as the fibronectin binding proteins. Recently, the role of secreted staphylococcal factors that were initially identified by virtue of their binding function with host proteins and ligands, has been reappraised in this regard. Among these, bacterial proteins without significant homology among each other, coagulase (Coa), the extracellular fibrinogen binding protein (Efb), the extracellular matrix binding protein (Emp), or the extracellular adhesive protein (Eap), are the most prominent ones to be associated with endovascular disease. Newly discovered interactions with host components may account for profound effects on immunmodulation and wound healing which are summarized in this short review and which ascribe an important role of these molecules in acute and chronic endo- and extravascular staphylococcal disease. Further research in the complex functional role of these "secretable expanded repertoire adhesive molecules" (SERAM) may not only help to increase our understanding in the pathogenesis of S. aureus infection but can specify novel targets for preventive or therapeutic strategies.