Staphylococcus aureus is a versatile and harmful pathogen in both hospital- and community-associated infections that range from superficial to systemic infections. S. aureus engages a multitude of mechanisms to subvert the innate immune response of the host, including inhibition of complement activation and neutralization of anti-microbial peptides. In addition, inflammatory cell and phagocyte recruitment is an integral part of the innate defense to staphylococcal infection and comprises a well-coordinated multi-step cascade of adhesive events. Recent and rapidly growing experimental evidence indicates the existence of a machinery of anti-adhesive and anti-chemotactic moieties of S. aureus that allow the bacterium to interfere with specific adhesive steps of the homing mechanism of leukocytes. Understanding the functions of these S. aureus-derived anti-inflammatory agents could also provide the platform for designing new therapies in several inflammatory and autoimmune diseases.