Loss of peritoneal function is a major factor leading to treatment failure in peritoneal dialysis (PD). To date, however, the relationship between the observed functional changes (reduction in ultrafiltration and changes in solute transport) and the structural alterations in the membrane have not been fully defined. Here we present data from the Peritoneal Biopsy Registry identifying and characterizing both changes in parietal peritoneal membrane thickness (degree of fibrosis) and vascular alterations (blood vessel degenerative changes) and relate these to the duration of dialysis. The genesis of functional changes in the membrane may be related to these vascular alterations. This issue is discussed in relation to the importance of nitric oxide and its synthetic enzymes in this process and its potential interaction with endothelial cell aquaporin function. It is widely believed that conventional acidic, lactate-buffered glucose-containing dialysis solutions contribute to both the structural and functional changes in the dialysed peritoneal membrane. The introduction of new more biocompatible solutions potentially allows us to reverse or attenuate these negative changes. This will be discussed in the context of our current understanding of peritoneal pathology in PD.