Cardiovascular disease accounts for 40% of all deaths among pediatric patients with end-stage renal disease (ESRD). ESRD has a particularly large influence on the cardiovascular system in children, as indicated by the more than 700-fold increased risk of cardiac death in affected individuals compared with healthy children of the same age. The prevalence of ESRD is low in children, however, and, consequently, few cardiac deaths occur. As a result, prospective follow-up studies of cardiac risk factors in the pediatric setting are lacking. Nevertheless, cross-sectional data on cardiac disease in children with ESRD have started to emerge. Arterial medial calcification is more prominent in children than classic atherosclerotic intimal calcification. Current data suggest that endothelial dysfunction appears early in renal failure in children, and is followed by arterial medial calcification. This calcification causes arterial wall stiffening and subsequently left ventricular hypertrophy. High systolic blood pressure and serum concentrations of intact parathyroid hormone, calcium and phosphate, as well as long-term dialysis, seem to be important risk factors for cardiovascular disease in pediatric patients with ESRD. These features are important targets for preventive intervention. This Review summarizes the currently available data on cardiovascular disease in children with renal failure.