Uraemic cardiomyopathy refers to the cardiac abnormalities that are seen in patients with chronic renal disorder (CKD). Historically, this term was wont to describe a severe cardiomyopathy that was related to end-stage renal disease and characterized by severe functional abnormalities that would be reversed following renal transplantation. In a modern context, uraemic cardiomyopathy describes the clinical phenotype of cardiac disease that accompanies CKD and is probably best characterized as diastolic dysfunction seen in conjunction with left ventricular hypertrophy and fibrosis. A multitude of things may contribute to the pathogenesis of uraemic cardiomyopathy, and current treatments only modestly improve outcomes. In this Review, we focus on evolving concepts regarding the roles of fibroblast growth factor 23 (FGF23), inflammation and systemic oxidant stress and their interactions with more established mechanisms such as pressure and volume overload resulting from hypertension and anemia, respectively, activation of the renin–angiotensin and sympathetic nervous systems, activation of the transforming growth factor-β (TGFβ) pathway, abnormal mineral metabolism and increased levels of endogenous cardiotonic steroids.