Urolithiasis affects 10%-15% of the population in their lifetime. After spontaneous passage or surgical treatment, a subset of these patients will have recurrent calculi. These recurrent stone events are significantly morbid and can potentially lead to serious chronic renal disease, thus prevention is a very important treatment goal. Fortunately, a reversible metabolic abnormality can be identified in over 90% of recurrent stone formers. Thus, a detailed metabolic evaluation using 24 hour urine collections and serum tests is indicated in patients at high risk for stone recurrence. Once the patient's underlying urinary physicochemical and physiologic derangements are defined, targeted medical therapy can be initiated in order to prevent growth of pre-existing stones and recurrent stone formation. In this paper, we provide a review of the currently available selective and nonselective pharmacologic treatments for urolithiasis. Furthermore, we discuss a number of investigational agents for kidney stone prevention. Although many of these agents are effective, there remain numerous clinical scenarios where currently available therapies are inadequate.