Renal calculus disease is a common cause of morbidity in industrialized societies, accounting for seven to 10 of every 1000 hospital admissions. Recent advances in surgical therapy have made operative therapy much less invasive while maintaining a high level of success. However, the need to reduce the incidence of this disease persists as more than one half of all stone formers will have recurrence. Although the etiology and therapy for several types of renal calculi are established, much remains unknown concerning the mechanisms of formation of the most prevalent form of renal calculi, calcium oxalate. This article reviews recent basic science and clinical research that attempts to identify the etiologies of renal calculus formation.