Coagulase-negative staphylococcus (CONS) infection is the most common bloodstream infection treated in neonatal and pediatric intensive care units and significantly impacts patient mortality and morbidity. Staphylococcus epidermidis is the most common CONS species isolated clinically and investigated for its pathogenicity and virulence. Difficulties exist in the differentiation of CONS infection from culture contamination in clinical specimens, as CONS is a common skin commensal. Most CONS isolates have the mecA gene and exhibit beta-lactam resistance. The glycopeptide antibiotics, such as vancomycin, are the mainstay in therapy, although resistance has been reported. Arbekacin, linezolid, and streptogramins are newer antibiotics being evaluated as alternatives to glycopeptides. Monoclonal and polyclonal antibodies have been developed against the cell-wall components of staphylococcus and may hold promise for immune prophylaxis and treatment of CONS infection.