Indwelling vascular catheters are a leading source of bloodstream infections in critically ill patients and cancer patients. Because clinical diagnostic criteria are either insensitive or non-specific, such infections are often overdiagnosed, resulting in unnecessary and wasteful removal of the catheter. Catheter-sparing diagnostic methods, such as differential quantitative blood cultures and time to positivity have emerged as reliable diagnostic techniques. Novel preventive strategies include cutaneous antisepsis, maximum sterile barrier, use of antimicrobial catheters, and antimicrobial catheter lock solution. Management of catheter-related bloodstream infections involves deciding on catheter removal, antimicrobial catheter lock solution, and the type and duration of systemic antimicrobial therapy. Such decisions depend on the identity of the organism causing the bloodstream infection, the clinical and radiographical manifestations suggesting a complicated course, the underlying condition of the host (neutropenia, thrombocytopenia), and the availability of other vascular access sites.