Given the irreversible nature of nephron loss, aging of the kidney is of special interest to diagnostic and toxicologic pathologists. There are many similarities among histologic lesions in aged human and canine kidneys, including increased frequency of glomerulosclerosis, interstitial fibrosis, and tubular atrophy. Unfortunately, there are few studies in which renal tissue from aged healthy dogs was adequately examined with advanced diagnostics-namely, transmission electron microscopy and immunofluorescence-so age-associated changes in canine podocytes and glomerular basement membranes are poorly characterized. An age-associated decrease in the glomerular filtration rate in humans and dogs (specifically small breed dogs) has been documented. Although lesions in aged rats and mice differ somewhat from those of aged dogs and humans, the knowledge gained from rodent models is still vital to elucidating the pathogenesis of age-associated renal disease. Many novel molecules implicated in renal aging have been identified through genetically modified rodent models and transcriptomic and proteomic analysis of human kidneys. These molecules represent intriguing therapeutic targets and diagnostic biomarkers. Likewise, influencing critical pathways of cellular aging, such as telomere shortening, cellular senescence, and autophagy, could improve renal function in the elderly.