The diaphragm serves as an anatomic border between the abdominal and thoracic cavities. Pathologic conditions traversing the diaphragm are often incompletely described and may be overlooked, resulting in diagnostic delays. Several routes allow abdominal contents or pathologic processes to spread into the thorax, including along normal transphrenic structures, through congenital defects in the diaphragm, through inherent areas of weakness between muscle groups, or by pathways created by tissue destruction, trauma, or iatrogenic injuries. A thorough knowledge of the anatomy of the diaphragm can inform an accurate differential diagnosis. Often, intraperitoneal pathologic conditions crossing the diaphragm may be overlooked if axial imaging is the only approach to this complex region because of the horizontal orientation of much of the diaphragm. Multiplanar capabilities of volumetric CT and MRI provide insight into the pathways where pathologic conditions may traverse this border. Knowledge of these characteristic routes and use of multiplanar imaging are critical for depiction of specific transdiaphragmatic pathologic conditions. © RSNA, 2020 • radiographics.rsna.org