Division of the mediastinum into specific compartments is beneficial for a number of reasons, including generation of a focused differential diagnosis for mediastinal masses identified on imaging examinations, assistance in planning for biopsies and surgical procedures, and facilitation of communication between clinicians in a multidisciplinary setting. Several classification schemes for the mediastinum have been created and used to varying degrees in clinical practice. Most radiology classifications have been based on arbitrary landmarks outlined on the lateral chest radiograph. A new scheme based on cross-sectional imaging, principally multidetector computed tomography (CT), has been developed by the International Thymic Malignancy Interest Group (ITMIG) and accepted as a new standard. This clinical division scheme defines unique prevascular, visceral, and paravertebral compartments based on boundaries delineated by specific anatomic structures at multidetector CT. This new definition plays an important role in identification and characterization of mediastinal abnormalities, which, although uncommon and encompassing a wide variety of entities, can often be diagnosed with confidence based on location and imaging features alone. In other scenarios, a diagnosis may be suggested when radiologic features are combined with specific clinical information. In this article, the authors present the new multidetector CT-based classification of mediastinal compartments introduced by ITMIG and a structured approach to imaging evaluation of mediastinal abnormalities. ©RSNA, 2017.