Catheter-related infections, exit-site-tunnel infections and peritonitis remain the Achilles heel of peritoneal dialysis. Although the overall incidence of peritoneal-dialysis-related infectious complications has been reduced since the introduction of the Y-set and double bag system, approximately one-fifth of peritonitis episodes are associated with catheter exit-site and tunnel infections. Since its development in 1968, the Tenckhoff catheter has become one of the most widely used peritoneal catheters, and many have proposed that a number of modifications have made it a better choice. Controversies concerning the effect on exit-site infections of catheter(s) with one or two cuffs, with straight, coiled, Swan-Neck, or other modifications led to the randomized controlled studies that are reviewed in this paper. Several studies have confirmed that mupirocin, applied at the exit-site as part of regular exit-site care, reduces the risk of S. aureus exit-site and tunnel infections. Recently, the emergence on a world-wide basis of mupirocin-resistant S. aureus (MuRSA) in peritoneal dialysis patients has brought this prophylactic strategy into question. However the low frequency of resistant organisms after four years of mupirocin prophylaxis suggests that we can continue its use with annual surveillance. Once established, exit-site infections may respond to appropriate treatment, but if not the only option may be catheter removal and replacement. Although peritonitis risk has decreased over the past decade, mainly due to improvements in connection technology, exit-site and tunnel infections have not. An exit-site infection that does not respond to treatment may lead to tunnel infection and to persistent peritonitis, which may require catheter removal and occasionally discontinuation of the peritoneal dialysis. Therefore it is important to be familiar with these factors that predispose to exit-site infection and to know how to prevent and to treat such infections. This review will discuss factors that predispose to catheter-related exit-site infections, techniques of exit-site care, and ways to prevent exit-site infection, with emphasis on S. aureus infections and their treatment.