Central venous catheters represent a major source of nosocomial bloodstream infections, which cause considerable excess morbidity. It is currently unknown to what extent these infections contribute to mortality. Most catheter-related infections (CRIs) are caused by Gram-positive organisms (mainly coagulase-negative staphylococci). Definite diagnosis of CRI necessitates removal of the catheter in most cases. However, the recently described technique of differential time to positivity may allow diagnosis of CRI with the catheter left in place. Removal of the catheter has been standard clinical practice for the management of CRI in the past and is still recommended in many cases. In specific situations, such as infections of implanted catheters with coagulase-negative staphylococci, a trial of catheter salvage may be justified. In catheter-related bloodstream infection Staphylococcus aureus and Candida spp., the catheter should be removed immediately, due to the high risk of metastatic infection and increased mortality. A clinical work-up for the detection of additional foci (including transesophageal echocardiography in S. aureus infections) is advisable in these cases. All CRIs should be treated with antibiotics to which the causative agent has been shown to be susceptible. In addition to systemic antimicrobial therapy, antibiotic lock therapy may be applied, especially in patients with implanted long-term catheters if catheter salvage is attempted.