Peritoneal sclerosis (PS) occurs in various clinical situations in Peritoneal Dialysis (PD) patients. Some degree of PS is often present in long-term PD patients, generally without clinical or functional consequences. At the other end of the spectrum of PS there is Sclerosing encapsulating peritonitis (SEP). Though infrequent, it is very severe. SEP is not a complication exclusive to PD; it is a syndrome related to many diseases of abdominal organs, some drugs and abdominal surgery. Remarkably, in many cases, the first symptoms of SEP appear months or years after the change from PD to HD has occurred. Today there is no full agreement about the microscopical findings of SEP or about the name of this syndrome: SEP or Encapsulating Peritoneal Sclerosis (EPS). The main etiopathogenetic factor for PS is the poor biocompatibility of PD solutions. In the etiopathogenesis of SEP, other factors in addition to the PD fluids have been suggested as possible causes (peritonitis, drugs, disinfectants, etc.). This paper reviews all the clinical aspects of PS and SEP: pathogenesis, clinical signs, diagnosis and therapy.