The way in which veterinary scientists think about and approach the study of genetic disease has not changed, but the tools available to veterinary scientists have and will continue to change, allowing us to study increasingly complex problems and to make more rapid advances in the context of simple problems. To put these advances in perspective, this article first gives a historical perspective on the approaches to studying genetic diseases, particularly in human beings, and then outlines the advances that have become possible with the availability of the dog genome sequence. The article then discusses two inherited defects that are associated with urolithiasis, in particular, those responsible for cystine and purine (uric acid and its salts) stone formation. Together, these two conditions illustrate the contemporary use of a broad range of genetic approaches.