Nephronophthisis is a chronic tubulo-interstitial nephritis which progress to terminal renal failure. It is an heterogeneous entity at the clinical as well as at the genetic level. There are three main clinical forms of nephronophtisis which have been associated with five gene defects. Juvenile nephronophtisis, the most frequent, progress to end stage renal failure before age 15. It is an autosomal recessive disease which is responsible for a urine concentration defect starting after age 2, failure to thrive and a progressive deterioration of renal function without signs of glomerular disease. Kidney size is normal. Histologic lesions concern tubular basement membranes which are thickened and multilayered or thinned. There is an associated interstitial fibrosis. Some children present with extrarenal symptoms: tapetoretinal degeneration (Senior-Loken syndrome), mental retardation, cerebellar ataxia, bone anomalies or liver involvement. Infantile nephronophtisis is a recessive autosomic tubulo-interstitial nephritis with cortical microcysts which progress to end stage renal failure before age 5. Adolescent nephronophtisis is a less frequent form of nephronophtisis. Medullary cystic disease is transmitted as an autosomic dominant trait. Clinical and histological signs are similar to nephronophthisis, but the disease progress later to terminal renal failure and is not accompanied by extra-renal symptoms. Several genes which are involved in nephronophtisis, encode proteins that localize in different cell compartments, in particular to the primary apical cilia, as it is the case for many other cystic kidney diseases.