Central venous catheter-related blood stream infection (CRBSI) is a major cause of morbidity and mortality in patients with end-stage renal disease treated with chronic hemodialysis. Risk factors include Staphylococcus aureus nasal colonization, longer duration of catheter use, previous bacteremia, older age, higher total intravenous iron dose, lower hemoglobin and serum albumin levels, diabetes mellitus and recent hospitalization. Symptoms that raise clinical suspicion of bacteremia in chronic hemodialysis patients are fevers and chills. When CRBSI is suspected, blood cultures should be obtained and empirical therapy with broad spectrum intravenous antibiotics initiated. The diagnosis of CRBSI is confirmed by isolation of the same microorganism from quantitative cultures of both the catheter and the peripheral blood of a patient that has clinical features of infection without any other apparent source. Gram-positive cocci, predominantly S. epidermidis and S. aureus, cause bacteremia in two-thirds of cases. Among the various approaches to management of CRBSI, removal and delayed replacement of the catheter, catheter exchange over a guidewire in selected patients, and the use of antimicrobial/citrate lock solutions have all been found to be promising for treatment and/or prevention; however, resolution of issues regarding selection, dose, duration and emergence of antibiotic-resistant organisms with chronic use of antibiotic lock solutions, as well as the safety of long-term use of trisodium citrate lock solutions, await further randomized, multicenter trials involving larger samples of hemodialysis patients.