During peritoneal dialysis, peritoneal cells are repeatedly exposed to a non-physiological hypertonic environment with high glucose content and low pH. Current sterile dialysis solutions cause inflammation in the submesothelial compact zone that leads to fibrosis, neoangiogenesis, progressive increases in solute transfer and even ultrafiltration failure. The peritoneal dysfunction will further be amplified with the development of an epithelial-to-mesenchymal transition of mesothelial cells and the dissipation of the osmotic driving force through increased area and solute transport that accompanied neoangiogenesis of the submesothelial microvasculature. The alteration in the peritoneal membrane will further be aggravated by peritonitis, advanced glycation end-products and glucose degradation products. Finally, there are emerging new data supporting a pro-inflammatory role of peritoneal adipocytes.