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This chapter provides a concise summary of the epidemiology, clinical significance, pathophysiology, diagnosis, and secondary preventive, medical management of kidney stone disease. Specific emphasis is placed on the contribution of diet on kidney stone risk and examples are given for potential dietary interventions to prevent kidney stones. Specific pharmacological therapies with their corresponding pathophysiological mechanism of action are reviewed. A practical diagnostic and therapeutic approach to the first and recurrent stone former is also discussed. Finally, a brief outlook into potential future directions for the prevention of kidney stone disease is provided, followed by a brief summary and concluding remarks.