Peritoneal dialysis (PD) has been established as a main renal replacement therapy for approximately 20 years. However, long-term peritoneal exposure to high glucose and other unphysiologic contents in the PD solution may potentiate the development of peritoneal fibrosing syndrome (PFS) in PD patients. PFS is composed of a wide spectrum of peritoneal alterations, which has been observed in PD patients. Molecular studies have shown that the fibrogenic effect of peritoneal mesothelial cells and the accompanying accumulation of extracellular matrix in the peritoneum are key events leading to PFS. In this review, we highlight the impact of PFS and its pathogenetic factors, including bioincompatible PD solution, multidisciplinary inflammatory mediators, and stimulatory cytokines in the peritoneal cavity. Current therapeutic strategies based on both clinical and basic evidence for the prevention or treatment of PFS are also reviewed.