Increases in glomerular size and thickening of the glomerular basement membrane are constant features that accompany growth and maturation in animals. Yet, some animals have chronic progressive nephropathy characterized by glomerulosclerosis and tubulointerstitial fibrosis. In these animals, clinically significant reductions in glomerular filtration rate may compromise health, particularly when other renal diseases occur concomitantly. Progressive thickening of the glomerular basement membrane is accompanied by changes in its composition, which may be responsible for changes in podocyte morphology and proteinuria. Within the tubulointerstitium, generalized accumulation of fibronectin and thrombospondin are accompanied by blood vessel proliferation. Fragility of these blood vessels with intermittent bleeding may initiate an inflammatory process that leads to focal areas of tubular atrophy and scarring. The pathogenesis of these lesions is unknown. Genetic background, sex, and environmental factors influence the tempo of progressive sclerosis, although these factors are not primary determinants of this lesion. This review highlights the structural changes that occur in the kidney with aging. Because the lesions are structurally similar, information gleaned from studies of aging animals should be relevant to understanding the loss of renal function that occurs in aging humans.