The formation of kidney stones depends, absolutely, on the nucleation of sparingly soluble salts - principally calcium oxalate - in the urinary tract. Under everyday conditions, urine is supersaturated with calcium oxalate, and occasionally we all pass calcium oxalate crystals in our urine. Yet, we do not all suffer from kidney stones. Why? Because urine contains a range of low and high molecular weight components that are able to inhibit the nucleation of crystals or, if crystals do nucleate, which prevent their enlargement by growth or aggregation into particles large enough to block the renal collecting tubules. The same molecules may also affect the likelihood that crystals attach to, or nucleate directly upon, the renal epithelium. Some are also occluded within the mineral bulk of urinary crystals, and by disrupting their crystalline structure they may assist their intra-renal degradation, dissolution, and disposal. This chapter reviews what is known about the possible, and paradoxical, roles of urinary low molecular weight components and macromolecules in the formation of stone mineral crystals and their potential functions in the development of human kidney stones.