Device-related bacteremia is the most frequent complication in patients with indwelling central venous catheter. Guidelines recommend treatment based on epidemiology and antimicrobial susceptibility tests, but catheter removal is advocated in the presence of particular clinical conditions or pathogen isolations. Anti-infective drugs might become less effective in the presence of pathogens with increases in minimal inhibitory concentrations or slime production, and sometimes catheter removal is not feasible, for example, in patients with limited vascular sites or in the presence of life-threatening clinical conditions. Catheter lock with anti-infective drugs (antibacterials or antifungals) or other substances with anti-infective properties (e.g., taurolidine, 70% ethanol, 2M HCl) might represent a possible rescue treatment in the presence of difficult-to-treat infections and/or when the device cannot be removed. In the present review, the authors summarize these possible therapeutic options. The aim of the report is not to perform a systematic review of the literature, but to give an 'easy to read' text for everyday practice.