Chronic kidney disease (CKD) has evolved as a possible new determinant of cognitive decline and dementia. This review outlines the presumed pathophysiology of cognitive decline in CKD, which consists of traditional and new vascular risk factors as well as nonvascular risk factors and metabolic and biochemical abnormalities within the central nervous system caused by CKD. The recent major cross-sectional studies and longitudinal studies - including one meta-analysis - that mostly suggest an association of cognitive decline and CKD are discussed. Finally, potential therapeutic strategies are presented.