Intravascular catheters are essential devices in the intensive care unit, yet catheter-related bloodstream infections (CR-BSI) are associated with increased morbidity and mortality, prolonged hospitalization, and increased medical costs. Management of a CR-BSI requires antibiotics, with or without catheter removal, depending on patient and etiologic factors. Because of the high frequency of staphylococcal infections, it is wise to use a glycopeptide empirically. Extra coverage for Gram-negative bacilli should be administered in severely ill or immunocompromised patients. Once culture and sensitivity results are known, antibiotic therapy can be more selective.