The prevalence of urolithiasis in humans is increasing worldwide; however, non-surgical treatment and prevention options remain limited despite decades of investigation. Most existing laboratory animal models for urolithiasis rely on highly artificial methods of stone induction and, as a result, might not be fully applicable to the study of natural stone initiation and growth. Animal models that naturally and spontaneously form uroliths are an underused resource in the study of human stone disease and offer many potential opportunities for improving insight into stone pathogenesis. These models include domestic dogs and cats, as well as a variety of other captive and wild species, such as otters, dolphins and ferrets, that form calcium oxalate, struvite, uric acid, cystine and other stone types. Improved collaboration between urologists, basic scientists and veterinarians is warranted to further our understanding of how stones form and to consider possible new preventive and therapeutic treatment options.