Medical device-associated infections, most frequently caused by coagulase-negative staphylococci, especially Staphylococcus epidermidis, are of increasing importance in modern medicine. Regularly, antimicrobial therapy fails without removal of the implanted device. The most important factor in the pathogenesis of medical device-associated staphylococcal infections is the formation of adherent, multilayered bacterial biofilms. There is urgent need for an increased understanding of the functional factors involved in biofilm formation, the regulation of their expression, and the interaction of those potential virulence factors in device related infection with the host. Significant progress has been made in recent years which may ultimately lead to new rational approaches for better preventive, therapeutic, and diagnostic measures.