The mesothelium is a specific group of cells having characteristics of both mesenchymal and epithelial cells. One of the most unique properties of these cells is a low proliferative capacity and a small number of achievable division. The purpose of this paper was to present the current state of knowledge on the causes of premature senescence of peritoneal mesothelial cells and to discuss the molecular events involved in this process. Particular attention was paid to the role of telomeres, the activity of senescence effectors at the level of the cell cycle, and the action of oxidative stress and transforming growth factor beta1. Moreover, the relationship between senescence of mesothelial cells and the aging of the organism as a whole, as well as the participation of senescent cells in the development of the intraperitoneal cancer metastasis was addressed.