The frequency, pathology, animal models, pathogenesis, clinical manifestations, diagnostic criteria, therapy and prevention of peritoneal sclerosis are reviewed. Many of these aspects have a bimodal configuration which suggests that peritoneal sclerosis, usually considered a single pathology in peritoneal dialysis, is actually two distinct nosological entities: simple sclerosis and sclerosing peritonitis. The former is very frequent, with minor anatomical alterations and low clinical impact; it is reproducible in animals by means of peritoneal dialysis, and is clearly due to the poor biocompatibility of peritoneal dialysis solutions. The latter is rare, with radical anatomical alterations and high mortality requiring valid methods of diagnosis, therapy and prevention; it can only be reproduced in animal models by means other than peritoneal dialysis and seems to be due to factors both related and unrelated to peritoneal dialysis.