Antibiotic lock therapy (ALT) - instillation of high concentrations of anti-microbial agent with or without anti-coagulant into the lumen of central venous catheters - is considered a valid conservative treatment for catheter-related bloodstream infection (CRBSI) in patients highly dependent on maintaining the catheter. Results from randomized controlled studies have indicated that the effectiveness of ALT is moderate, but recent findings from experimental studies and observational case series point to considerable efficacy and safety of this therapy, which is usually associated with concomitant systemic treatment. In this article, the current knowledge about ALT for patients with CRBSI is reviewed and discussed, with emphasis on existing controversies and the results obtained according to the various uses of the catheters and the etiologies of infection.