Staphylococcus epidermidis and other coagulase-negative staphylococci (CNS), often dismissed previously as culture contaminants, are assuming great clinical importance as true pathogens. CNS infections are associated with indwelling foreign bodies and increase along with increasing use of catheters and artificial devices inserted through the skin. CNS from nosocomial infections, particularly S. epidermidis, are usually resistant to multiple antibiotics, with more than 80% resistant to methicillin. Methicillin-resistant. epidermidis (MRSE) can become resistant to all β-lactams, cephalosporins, and carbapenems by the aquisition of a chromosomal mecA gene, which encodes penicillin-binding proteins 2a that has low affinity for β-lactams. S. epidermidis universally attaches to surface of indwelling artificial devices and catheters and produces extracellular polysaccharides, resulting in the formation of a biofilm. Biofilms increase resistance of S. epidermidis to antimicrobial agents and the potential to cause infections in patients with indwelling medical devices. The drug of choice for MRSE infection is glycopeptide antibiotics (e.g. vancomycin and teicoplanin) and cure rates have been improved by addition of gentamicin or rifampin. Recently developed noble antibiotics for Gram-positive bacteria, quinupristin/dalfopristin and linezolid, will play an important role in the treatment of serious MRSE infections. However, antibiotics alone often fail for cure and removal of indwelling medical devices may be crucial.