<p>People with chronic kidney disease who require maintenance dialysis characteristically experience accelerated and aggravated cognitive decline compared with those with advanced kidney disease who are not receiving this form of kidney replacement therapy. This effect is inadequately appreciated, but of crucial importance to patients, their carers and the health-care systems that support them. Although many of the comorbid conditions prevalent in this patient population have the potential to affect brain structure and function, an evolving body of evidence indicates that the dialysis therapy itself has a central role in the pathophysiology of progressive cognitive impairment. Both haemodialysis and peritoneal dialysis are associated with structural and functional changes in the brain that can lead to characteristic short-term symptoms, such as headache, confusion, delirium and brain fog, as well as long-term reductions in cognitive functional ability. Here, we explore the mechanisms, both established and putative, underlying these effects and consider approaches to addressing this issue with both single and complex therapeutic interventions.</p>