The development of peritoneal dialysis has been paralleled by a growing interest in establishing suitable experimental models to better understand the functional and structural processes operating in the peritoneal membrane. Thus far, most investigations have been performed in rat and rabbit models, with mechanistic insights essentially based on intervention studies using pharmacological agents, blocking antibodies, or transient expression systems. Since the body size of a species is no longer a limiting factor in the performance of in vivo studies related to peritoneal dialysis, it has been considered that mice, particularly once they have been genetically modified, could provide an attractive tool to investigate the molecular mechanisms operating in the peritoneal membrane. The purpose of this review is to illustrate how investigators in peritoneal dialysis research, catching up with other fields of biomedical research, are increasingly taking advantage of mouse models to provide direct evidence of basic mechanisms involved in the major complications of peritoneal dialysis.