Numerous systems have been created to divide the mediastinum into specific compartments for the purposes of generating a focused differential diagnosis for masses and other abnormalities identified on imaging, planning for biopsies and surgical interventions, and facilitating communication between health care professionals in a multidisciplinary setting. Most have focused on imaging and are based on arbitrary landmarks delineated on the lateral chest radiograph. The International Thymic Malignancy Interest Group has developed a classification system based on cross-sectional imaging, defining specific prevascular, visceral, and paravertebral compartments, that has been accepted as a new standard and is the topic of this review.