Coagulase-negative staphylococci (CNS), which historically have been viewed as contaminants when recovered in culture media, are now recognized as opportunistic pathogens of increasing importance in hospital-acquired infections. They are frequently found colonizing prosthetic devices and intravenous lines. CNS are capable of producing a variety of infections including deep-seated infections such as endocarditis and meningitis. Staphylococcus epidermidis is the most commonly isolated CNS and it appears to be the most resistant to antibiotics, making antimicrobial therapy challenging. Treatment of the infection will very often require removal of a prosthetic device, if present. An adequate infection control program is imperative in prophylaxis against this infection.