Congenital anomalies of the kidney and urinary tract are the major cause of ESRD in childhood. Children with a solitary functioning kidney form an important subgroup of congenital anomalies of the kidney and urinary tract patients, and a significant fraction of these children is at risk for progression to CKD. However, challenges remain in distinguishing patients with a high risk for disease progression from those patients without a high risk of disease progression. Although it is hypothesized that glomerular hyperfiltration in the lowered number of nephrons underlies the impaired renal prognosis in the solitary functioning kidney, the high proportion of ipsilateral congenital anomalies of the kidney and urinary tract in these patients may further influence clinical outcome. Pathogenic genetic and environmental factors in renal development have increasingly been identified and may play a crucial role in establishing a correct diagnosis and prognosis for these patients. With fetal ultrasound now enabling prenatal identification of individuals with a solitary functioning kidney, an early evaluation of risk factors for renal injury would allow for differentiation between patients with and without an increased risk for CKD. This review describes the underlying causes and consequences of the solitary functioning kidney from childhood together with its clinical implications. Finally, guidelines for follow-up of solitary functioning kidney patients are recommended.