The subperitoneal space is a large potential space in the abdominal cavity created during embryogenesis. It plays an important, although often underestimated, role in the spread of intra-abdominal disease. The various mesenteric folds and ligaments serve as communicating pathways between compartments but sometimes act as barriers to the spread of disease. The authors describe the anatomic features of the subperitoneal space in detail and illustrate the interconnections between organs and compartments by means of case studies. An appreciation of the role of the subperitoneal pathways allows accurate interpretation of complex images and improved diagnostic accuracy.