Background: The success of peritoneal dialysis on the short-term is mainly dependent on the prevention of infectious and technical complications. The mid-term results will to a large extent be determined by the ability to remove enough uraemic toxins to prevent uraemic complications and malnutrition. The long-term challenge is the prevention of the development of structural abnormalities of the peritoneum leading to ultrafiltration failure and sometimes peritoneal sclerosis. Methods: A review of the literature on the possibilities to increase the removal of uraemic waste products from the body, and on strategies to detect and prevent deteriorations of the peritoneal membrane during long-term dialysis treatment. Results and Conclusions: Improved efficacy and safety of peritoneal dialysis on the midterm can be achieved by individualization of the dialysis prescription taking residual renal function especially into account. Early start of dialysis might reduce the progression rate of renal function deterioration, but exposes the peritoneum to bio-incompatible dialysis solutions for a longer time. The long-term alterations in the peritoneal membrane are probably mainly caused by the continuous exposure to dialysis fluids, especially glucose, and perhaps the combination of low pH with lactate. The implications of long-term continuous ambulatory peritoneal dialysis using only more biocompatible dialysis fluids are not clear. To improve the efficacy and safety of peritoneal dialysis, careful monitoring of patients and dialysis is mandatory. This should include 24-hour urine collections and 24-hour dialysate collections to calculate the residual glomerular filtration rate and adequacy parameters. A peritoneal membrane function test should be done regularly with 3.86% glucose dialysate, including determinations of dialysate Na<sup>+</sup> and cancer antigen 125 to detect patients who are at risk for the development of structural abnormalities of the peritoneum.