Long-term central venous catheters are essential for the treatment of patients requiring long-term intravenous medications, blood product support, and total parenteral nutrition. Thrombosis and infection, complications commonly associated with the use of these devices, represent an important cause of morbidity and mortality. To reduce the incidence of device removal because of persistent central venous catheter-related infection, the novel use of a highly concentrated antibiotic “lock” solution instilled into the catheter lumen for a defined time has been explored. This technique has been successful in numerous small uncontrolled studies, suggesting that an antibiotic lock may be effective in salvaging infected central venous access devices. Currently, the Centers for Disease Control and Prevention Guidelines on the management of central venous access device infections support the use of this technique only for patients requiring long-term access who repeatedly experience catheter-related bloodstream infections despite stringent catheter care. Additional studies are warranted to support these preliminary data.