To diminish the risk of serious complications from catheter-related bacteremias or fungemias, an optimized diagnosis and antimicrobial therapy is essential and early catheter removal should be considered. Prompt removal of the catheter and targeted antimicrobial treatment remains a common approach for febrile episodes in patients on total parenteral nutrition. However, novel tools allow diagnosis of catheter-related infections with the catheter in situ. Moreover, many of the established catheter-related infections caused by coagulase-negative staphylococci can successfully be treated with the catheter still in place. The use of these advanced management options depends widely on the resource of the microbiology laboratory as well as the type of catheter and severity of the patient's disease.