Long-term survival of children with end-stage renal disease (ESRD) has increased in the last 20 years, but the mortality rate remains high. Cardiovascular disease accounts for 40 to 50% of all deaths, infectious disease for about 20%. A prolonged period of dialysis versus having a renal graft and persistent hypertension are mortality risk factors. The prevalence of the various morbidities is high among those who have reached adulthood. Nearly 50% of all these patients suffer from left ventricular hypertrophy and life-threatening vascular changes; nearly one third has clinical signs of metabolic bone disease. This accounts for both dialysis and transplant recipients. The chance of getting cancer is increased ten times compared to the general population; skin cancer and non-Hodgkin lymphomas are most commonly reported. A long period of dialysis at childhood is associated with impairment of both cognitive and educational attainment. However, despite all these negative outcomes, the health perception of young adults with childhood onset ESRD is positive. Research and therapy in children with ESRD should focus not only on prevention of graft failure, but also on prevention of co-morbidity, especially cardiovascular disease, life-threatening infections and malignancies. Early transplantation, more extended forms of frequent hemodialysis in those who can not be transplanted, a more rigorous treatment of hypertension, avoidance or at least dosage reduction of calcium-containing phosphate binders, reduction of the chronic inflammatory state, and tailor made anti-rejection therapy after transplantation may all be targets to improve the outcome in future patients.