Coagulase-negative staphylococci (CNS) are normal inhabitants of human skin and mucous membranes. They have long been dismissed as culture contaminants, but now the potentially important role of CNS as pathogens and their increasing incidence has been recognized. Approximately 55-75% of nosocomial isolates is methicillin resistant. CNS were the first organisms in which glycopeptide resistance was recognized. In the immunocompetent host, CNS endocarditis and urinary tract infections with Staphylococcus saprophyticus are the most common CNS infections. Other patients are usually immunocompromised, with indwelling or implanted foreign bodies. CNS account for approximately 30% of all nosocomial blood stream infections. The majority of these concern catheter-related sepsis. Other important infections due to CNS include central nervous system shunt infections, endophthalmitis, surgical site infections, peritonitis in patients with continuous ambulatory peritoneal dialysis and foreign body infections. CNS are rarely associated with mastitis in humans. Staphylococcus lugdunensis is more pathogenic than other CNS as it expresses several potential virulence factors. The distinction between clinically significant, pathogenic and contaminating isolates is a major problem. Several studies show clonal intra and inter hospital spread of Staphylococcus epidermidis strains which suggests that infection control measures may be necessary for multiresistant CNS isolates as for methicillin resistant Staphylococcus aureus. As a result of medical progress, mainly due to the use of invasive and indwelling medical devices, CNS are now a major cause of nosocomial and health-care related infections.