Recent work in nephrolithiasis has benefited from 2 special kinds of imaging: endoscopic study of patient kidneys with high-quality instruments, and examination of stones with microscopic computed tomography (micro CT). The combination of these has provided new evidence that there is more than 1 mechanism by which stones are retained in the kidney until they achieve sizes to be clinically relevant. This review describes what is known about the formation of stones on Randall’s plaque, the formation of stones on ductal plugs and the ways in which stones may grow in free solution within the calyceal or pelvic spaces. Studies of urolithiasis need to recognize that any group of “stone formers” likely includes patients who differ fundamentally regarding which mechanism of stone formation is the primary route for their stones. Separation of patients on the basis of which mechanism (or combination of mechanisms) underlies their disease will be important for advancing research in the area of urolithiasis.