The pathogenesis, diagnosis, and management of central venous catheter infections differ between short-term and long-term catheters. This review summarizes available data regarding the diagnosis and management of catheter-related bloodstream infections (CRBSIs) associated with long-term catheters. A review of various diagnostic modalities is provided, including methods of CRBSI diagnosis for catheters that are retained. Management of CRBSIs for long-term catheters is also addressed, with an emphasis on differentiating infections that require catheter removal from those that may allow catheter salvage. Data regarding catheter salvage with use of antibiotic lock therapy are also reviewed.