Peritoneal dialysis is now utilized as a renal replacement therapy modality in a substantial percentage of patients with end-stage renal disease, with excellent short-term patient and technique survival rates. However, the potential complications associated with longer-term therapy, such as ultrafiltration failure or encapsulating peritoneal sclerosis, have led to raise some concern about peritoneal dialysis as an adequate mode of treatment of end-stage renal disease in the long term. In the last decade, a substantial amount of information has been gathered on the characteristics of the peritoneal membrane at the onset of peritoneal dialysis, and on the anatomical and pathophysiologic changes that occur with long-term peritoneal dialysis. I will review this subject with a special focus on the various strategies that can help protect the peritoneal membrane during peritoneal dialysis so as to allow peritoneal dialysis to succeed as a long-term dialysis modality.