Calcium oxalate is now the main form of nephrolithiasis in most countries. It may result from unfrequent genetic or acquired diseases, the diagnosis of which being of a major importance for an effective treatment to protect against stone recurrence and renal failure. A more common cause of calcium oxalate nephrolithiasis is the conjonction of inappropriate dietary habits and/or low diuresis in subjects who are particularly susceptible to these factors because of an inherited trait. In such cases, an identification of biological factors involved in the crystallization risk related to the dietary factors is required in order to advise efficient preventive measures against stone recurrence. The use of drugs should be limited to nephrolithiasis that cannot be controlled by diuresis and dietary advices.