Objective: To evaluate the evidence regarding the use of ethanol lock therapy (ELT) for catheter-related bloodstream infection (CRBSI) prophylaxis and treatment. Data Sources: A literature search was conducted using PubMed (August 2003-January 2013) with search terms: ethanol lock, ethanol locks, ethanol lock therapy, prophylaxis, prevention, catheter-related bloodstream infection, and catheter-related infection. Additional sources were identified through a subsequent review of relevant articles. Study Selection and Data Extraction: All English-language studies with >1 patient and a primary outcome of rates of infection, clinical cure, catheter removal or line salvage were evaluated. Studies where ELT was not used for CRBSI prophylaxis or treatment, review articles, and in vitro studies were excluded. Data were abstracted through an independent review of all articles by 2 authors. Discrepancies were discussed and resolved. Data Synthesis: 13 prophylaxis studies evaluated 617 patients; all studies reported decreased rates of infection and catheter removal with ELT. The ELT regimen associated with the most consistent benefit was 70% ethanol, a 2- to 4-hour dwell time, and daily exchange for ≥1 month. 9 treatment studies evaluated 213 catheters, with 90% (192/213) cure and 84% (179/213) line salvage. ELT was always used in combination with systemic antibiotics. The most common ELT treatment regimen was 70% ethanol, a 12- to 24-hour dwell time, and a duration of 1-5 days. No serious adverse events were reported. Conclusion: The current literature suggests that prophylactic ELT decreases the rates of infection and catheter removal, and ELT treatment appears efficacious in combination with systemic antibiotics.