Catheter-related bloodstream infections are often difficult to treat because they are caused by organisms that embed themselves in a bio film layer on the catheter surface, resulting in an increased resistance to antimicrobial agents. Systemic antibiotics are usually administered but, although generally effective in eliminating circulating bacteria, they frequently fail to sterilize the line, leaving the patient at a continuing risk of complications or recurrence. A successful approach to managing these infections requires making an appropriate decision regarding whether the catheter should be removed or retained using antibiotic lock therapy; and choosing the type and duration of antimicrobial therapy based on the type of organism and its resistance pattern. Studies that have evaluated antibiotic lock therapy have varied in the types of antibiotics and concentrations used, the addition of heparin to the solutions, and dwell times in the catheter lumen. Guidelines from the Infectious Diseases Society of America include use of antibiotic lock therapy as a therapeutic option for intraluminal infections when the device is not removed and, although not routine, as prophylaxis for catheter-related infection in select patient populations. However, there are no published guidelines on the concentration of heparin or antibiotics that should be used, and minimal published data on the stability of heparin combinations with antibiotics. It is to be hoped that antibiotic locks will be subject to randomized controlled trials of sufficient power to confirm or refute their use.