In the United States, there is a large and growing population of patients undergoing dialysis because of end-stage renal disease (ESRD). These patients present special management considerations for dentists, including antibiotic prophylaxis for the prevention of bacterial endocarditis (BE). ESRD patients, particularly those with an arteriovenous shunt for hemodialysis access, are predisposed to valvular endocarditis. Thus, BE prevention is the primary goal of antibiotic prophylaxis prior to dental or other invasive procedures in these patients. Bacteremia may predispose to infection of synthetic vascular access grafts, although this form of endovascular infection in ESRD patients has not been as well-characterized as BE. Antibiotic prophylaxis may be of some benefit for prevention of synthetic graft infections as well as BE. Poor dentist and physician compliance with BE prophylaxis regimens, as well as errors in dosing, timing, or duration of prophylaxis, have been reported. These problems are of particular concern in the treatment of chronically ill patients. In this article, we review the rationale for prophylactic antibiotic therapy prior to dental procedures in ESRD patients with vascular access. We also elaborate on the current American Heart Association guidelines for BE prophylaxis, and address special considerations for ESRD patients.