Few data exist on the prospects in adulthood for children on chronic renal replacement therapy (RRT). This article summarizes the results of a comprehensive Dutch long-term follow-up study performed in 2000 and 2010 of patients with RRT onset at age <15 years between 1972 and 1992. After a median of 25.5 RRT years, patients had stayed 23% of RRT time on dialysis. We observed a 30 times greater mortality risk compared with age-matched peers with cardiovascular disease (CVD) as the main cause of death during 1972-2000 and infections during 2000-10. The observed shift towards infections was associated with more RRT time with a graft and receiving a stricter CVD protective treatment. For patients >40 years of age, motor disabilities affecting routine activities, skin cancer and severe fatigue were the most disabling sequelae. After 30 years of transplantation, 41% of the survivors had developed cancer, a life-threatening form of squamous cell skin carcinoma being most prevalent. Important delays in autonomy development and educational attainment and a relatively high level of unemployment were observed. Transplanted patients reported a good mental and physical quality of life, but the latter tended to decrease over time. A long period of dialysis was associated with all adverse somatic and psychosocial outcomes. Paediatric nephrologists should aim for transplantation at the earliest possible time and focus on autonomy and educational attainment. Nephrologists should focus on strict CVD prevention, adjustment of immunosuppression to the lowest possible dose and surveillance of malignancy-associated viral infections in patients with childhood end-stage renal disease.