The extrapleural space (EPS) is an anatomic space at the periphery of the chest that can be involved in a number of disease processes. This space lies between the inner surface of the ribs and the parietal pleura and contains adipose tissue, loose connective tissue, lymph nodes, vessels, endothoracic fascia, and the innermost intercostal muscle. It is often overlooked on cross-sectional imaging studies and almost invariably overlooked on conventional radiographic studies. At conventional radiography, the EPS occasionally can be seen when there is extrapleural fat proliferation, which might be confused with pleural thickening or pleural effusion. Knowledge of the normal anatomy of the EPS depicted at computed tomography (CT) and of the relationship of the EPS with parenchymal, pleural, and chest wall processes is key to the detection of extrapleural abnormalities. Disease entities that most commonly affect the EPS include chronic inflammatory disorders, infection, trauma, and neoplasms. Chronic inflammatory conditions and infectious processes of the lungs and pleurae induce adipocyte proliferation adjacent to the inflamed tissue, resulting in increased extrapleural fat. Chest wall trauma with extrapleural hematoma formation causes characteristic CT findings that enable differentiation of the extrapleural hematoma from hemothorax and warrant a different treatment approach. Extrapleural air is commonly seen in patients with pneumomediastinum and should be distinguished from pneumothorax because it requires a different treatment approach. Intrathoracic neoplasms can cause an increase in the attenuation of normal extrapleural fat owing to pleural inflammation, lymphatic obstruction, lymphangitic spread, or direct invasion by tumor. The normal and pathologic appearances of the EPS, as depicted at thoracic CT, and the differential diagnosis of findings in the EPS are reviewed. ©RSNA, 2017.