<p>Although classically a disease of male preponderance, scrutiny of the available data on&nbsp;nephrolithiasis&nbsp;reveals substantial epidemiological discrepancies between males and females, suggesting sex-based&nbsp;pathophysiology&nbsp;underlying this disease.&nbsp;Furthermore, sex-based differences may exist in underlying urinary risk factors, presentation, and treatment response. Recognizing these differences will be essential to further understand the multitude of etiologies of kidney stone disease and aid in developing appropriately designed comparative effectiveness trials.</p>