Supersaturation is the driving force behind crystal formation in the kidneys. It can, however, result only in the formation of crystals which can be harmlessly expelled. For stone formation, crystals must form in the kidneys and be retained there, which is indeed a rare occurrence. Crystalluria is common while stone formation is not. Only pathological changes in the kidneys including renal injury and dysfunction can accomplish crystal retention. Lethal epithelial cellular injury promotes crystal nucleation, aggregation and retention. Sub-lethal injury or dysfunctional cells may produce ineffective crystallization modulators and localized areas of supersaturation in the interstitium. The former will affect crystallization in the urine while the latter may cause precipitation in the interstitium and development of Randall’s plaques.