Staphylococcus aureus infections are a major cause of morbidity and hospitalization in dialysis patients. The risk of infection relates to the type of access. Patients with acute hemodialysis (HD) catheters are at the greatest risk of S. aureus bacteremia, followed by tunneled HD catheters, and grafts. Patients with a fistula have a rate similar to that of peritoneal (PD) patients. In PD patients, however, S. aureus is the second most common cause of peritonitis, is often associated with a catheter infection, and frequently requires catheter removal for resolution. S. aureus infections in dialysis patients are much more common in nasal carriers. S. aureus moves from the nasal reservoir to the hands and skin, and from there to infect the access. Therefore, prevention of infection can be aimed at treating the carriage or in applying antibiotics at the catheter exit site, thus preventing colonization and subsequent infection of the catheter. For HD patients with a permanent access (either fistula or graft), intranasal mupirocin, twice a day for 5 days followed by a once weekly application, is effective in reducing the risk of S. aureus bacteremia. Cost analysis indicates that treating all patients would result in more cost savings than treating just carriers. For patients with acute HD catheters, exit site mupirocin applied as part of routine care during each HD treatment, reduces the risk of S. aureus exit site infection and bacteremia. For PD patients, S. aureus infections can be diminished by using mupirocin at the exit site as part of daily exit site care. Prophylaxis against S. aureus is under utilized in dialysis patients and, if implemented, could lower the rate of these serious infections.