The symptom complex of renal colic is common, and the central feature is flank pain with or without radiation to the groin. Acute ureteral obstruction causes an increase in hydrostatic pressure within the urinary system and is the inciting factor in the generation of acute flank pain of renal origin. The differential diagnosis for acute flank pain is broad and includes both urologic and non-urologic entities, with gastrointestinal, vascular, and gynecologic processes accounting for many of the non-urologic causes. The diagnostic workup begins with a complete history and physical exam with appropriate laboratory assessment. Imaging plays a critical role, with computed tomography (CT) serving as the ultimate cornerstone of the diagnostic algorithm. The overarching goal of the workup is to efficiently recognize signs of serious illness (e.g., fever, hypotension, peritonitis) and rapidly intervene to avoid patient morbidity.