Exit-site infection remains one of the major peritoneal dialysis (PD) complications. The evolution of this infection can be secondary peritonitis and or peritoneal catheter loss. In this paper, the natural history of exit-site infection is described. In addition, the possible preventive measures are reviewed and analyzed. In particular surgical technique, perioperative protocols and the care of the exit-site are examined. Particular attention was devoted to the clinical role of staphylococcus (S.) nasal carriers and to the possible prevention of Staphylococcus Aureus infections in these patients. When infection occurs, different diagnostic tools could be appropriate, based on the amount of damage, the clinical symptoms and the medical history. Medical therapy should be selected based on international guidelines and prompt and timely intervention can be the cornerstone of successful therapy. In the case of infections resistant to local and parenteral antibiotic administration, the catheter should be removed. However, good results have been reported by removing part of the catheter and outer cuff; therefore, avoiding hemodialysis (HD) and reducing hospitalization and the need for surgery. When the peritoneal catheter requires removal, the possibility of removing and replacing the peritoneal catheter in a single operation requires consideration, to improve the quality of life and reduce the distress of the patient.