Catheter-related bacteremia is a major cause of morbidity among hemodialysis patients. This article reviews the medical literature regarding the treatment and prophylaxis of catheter-related bacteremia. Bacterial biofilm that forms in the catheter lumen is the source of catheter-related bacteremia. Treatment with systemic antibiotics alone fails to definitively eradicate the infection in most patients. Catheter-related bacteremia can be managed by either catheter removal with delayed placement of a new catheter or exchange of the infected catheter with a new catheter over a guidewire. More recent studies suggested that instillation of an antibiotic-anticoagulant lock into the catheter lumen, as an adjunct to systemic antibiotic therapy, can cure approximately two thirds of catheter-related bacteremias without requiring catheter replacement. The frequency of catheter-related bacteremia may be reduced by using tunneled, rather than nontunneled, dialysis catheters and strict aseptic technique. In addition, several pharmacological measures may be useful for prophylaxis against catheter-related bacteremia. These include application of an antimicrobial ointment (mupirocin or polysporin [Pfizer, New York, NY]) to the catheter exit site or instillation of an antimicrobial solution (gentamicin or taurolidine) into the catheter lumen. Subcutaneous dialysis devices do not reduce the frequency of catheter-related bacteremia unless an antimicrobial solution is instilled into the device. The development and widespread adoption of effective approaches to the treatment and prophylaxis of catheter-related bacteremia will dramatically reduce the morbidity and economic burden associated with this complication.