Companion dogs are increasingly recognized as translational models for studying human physiology and disease. Unlike conventional or genetically engineered laboratory models, dogs are outbred, immunocompetent animals that spontaneously develop complex diseases whose pathogenesis and environmental exposures commonly overlap with those of humans. These distinctive features create opportunities to study mechanisms of disease, progression, and therapeutic responses under conditions that more closely resemble clinical reality. This review highlights evidence for the translational relevance of canine models across multiple therapeutic areas. We further discuss how advances in genomics, transcriptomics, spatial biology, in vitro, and in silico model systems are expanding the translational utility of canine models for applications in human medicine. Although important species differences must be carefully weighed, dogs represent a uniquely valuable comparative model for elucidating disease mechanisms, informing drug development, and accelerating the translation of scientific discoveries to human medicine.