The urine of healthy people is supersaturated with different calcium salts. Nevertheless, not everyone forms stones. This is partly because human urine contains substances that inhibit nucleation, growth, and aggregation of stone crystals. Some of these substances have a low molecular weight such as citrate, which seems to be the most powerful, and others are macromolecular substances of more than 10 kD, glycosaminoglycans, and proteins. The bulk of inhibitory activity has been ascribed to proteins. Recently, several proteins have been chemically characterized, their site of synthesis defined, their excretion rates measured, and their relation to recurrent renal stone formation specified. Nevertheless, it will be necessary to establish the role of each protein.