Despite improvements in the delivery of care, the annual all-cause mortality rate for end-stage renal disease (ESRD) patients is still around 220 deaths per 1000 at risk patient-years. Infection-related causes are second only to cardiovascular events as a cause for mortality among ESRD patients. Almost two-thirds of all ESRD patients will require hemodialysis and they are at the highest risk for bloodstream infections. An effective method for reducing bloodstream infections is increasing the use of fistula for dialysis access, but, for a significant number of patients, catheter access is inevitable. Several interventions have been studied that primarily involves the application of antimicrobials at the catheter exit site. Other interventions include the use of antibiotic lock solutions, which have resulted in the development of antibiotic resistance. Novel connecting devices may be of use in the future, but studies are still needed to show their efficacy at preventing catheter-related bloodstream infections among hemodialysis patients. As insertion sites can be limited in hemodialysis patients, treatment of certain catheter-related bloodstream infections can be amenable to catheter retention as long as both systemic antibiotic and antibiotic lock therapies are also initiated. Until more data are available, catheter removal followed by systemic therapy is preferred for infections involving Staphylococcus aureus, Pseudomonas species, Enterococcus species, and Candida species.