Imaging plays a major role in the evaluation of patients who present to the emergency department with acute left upper quadrant (LUQ) pain. Multidetector computed tomography is currently the primary modality used for imaging these patients. The peritoneal reflections, subperitoneal compartment, and peritoneal spaces of the LUQ are key anatomic features in understanding the imaging appearance of acute diseases in this area. Diseases of the stomach, spleen, pancreas, and splenic flexure are encountered in patients with acute LUQ pain. Optimization of the imaging protocol is vital for accurate diagnosis and characterization of these diseases in the acute setting.