An increasing proportion of central line-associated bloodstream infections (CLABSIs) are seen in outpatient settings. Many of such infections are due to hemodialysis catheters (HD-CLABSIs). Such infections are associated with substantial morbidity, mortality, and excess healthcare costs. Patients who receive dialysis through a catheter are 2–3 times more likely to be hospitalized for infection and to die of septic complications than dialysis patients with grafts or fistulas. Prevention measures include minimizing the use of hemodialysis catheters, use of CLABSI prevention bundles for line insertion and maintenance, and application of antimicrobial ointment to the catheter exit site. Instillation into dialysis catheters of antimicrobial solutions that remain in the catheter lumen between dialyses (antimicrobial lock solutions) has been studied, but it is not yet standard practice in some dialysis units. At least 34 studies have evaluated the impact of antimicrobial lock solutions on HD-CLABSI rates. Thirty-two (94%) of the 34 studies demonstrated reductions in HD-CLABSI rates among patients treated with antimicrobial lock solutions. Recent multicenter randomized controlled trials demonstrated that the use of such solutions resulted in significantly lower HD-CLABSI rates, even though such rates were low in control groups. The available evidence supports more routine use of antimicrobial lock solutions as an HD-CLABSI prevention measure in hemodialysis units.