The prevalence of urolithiasis has been increasing for the past few decades in industrialized nations. Uric acid calculi account for a significant percentage of urinary stones. Certain risk factors may be involved in the pathogenesis of uric acid nephrolithiasis, including hyperuricosuria, low urinary volume, and persistently low urinary pH. Patients with medical conditions that promote profound hyperuricosuria are at high risk of developing uric acid calculi. These conditions include chronic diarrheal states; myeloproliferative disorders; insulin resistance, including diabetes mellitus; and monogenic metabolic disorders, such as Lesch-Nyhan syndrome. Computed tomography can provide a definitive diagnosis. Except in cases in which there is severe obstruction, progressive azotemia, serious infection, or unremitting pain, the initial treatment of patients with uric acid nephrolithiasis should be medical dissolution therapy because this approach is successful in the majority of cases. A thorough review of the epidemiology and pathophysiology of uric acid nephrolithiasis is crucial for the diagnosis, treatment, and prevention of stones in patients with this condition.