The American Urological Association Nephrolithiasis Guidelines Panel recently conducted a critical meta-analysis of the existing literature to determine the optimal management for staghorn calculi. This article briefly discusses the pathophysiology of staghorn calculi and, based on the panel’s recommendations, examines the alternative medical treatments (eg, chemolysis) and surgical treatments (eg, shock wave lithotripsy, open surgery, ureteroscopy, and percutaneous nephrolithotomy) available for staghorn patients. Considering the various modalities for staghorn disease, percutaneous nephrolithotomy should be the first-line treatment for most patients based on its superior efficacy and low morbidity.