A variety of diseases can arise from the normal contents of the retrotracheal space or from adjacent structures. Mediastinal diseases in the retrotracheal space typically manifest radiographically as a contour abnormality or an area of increased opacity, although computed tomography (CT) or magnetic resonance (MR) imaging is usually required for diagnosis. The most common aortic arch anomaly, a right subclavian artery that originates from an otherwise normal left-sided aortic arch, appears at posteroanterior chest radiography as an obliquely oriented soft-tissue area of increased opacity that extends superiorly to the right from the superior margin of the aortic arch. CT and MR imaging can reveal associated vascular or mediastinal abnormalities. Aortic aneurysms and pseudoaneurysms can manifest radiographically as fusiform or saccular masslike lesions that protrude into the retrotracheal space. Thoracic MR imaging and spiral CT angiography are the diagnostic procedures of choice for evaluating diverse pathologic conditions of the thoracic aorta. Esophageal diseases can manifest as an abnormality in the retrotracheal space, which may be the initial clue to the diagnosis. At CT, lymphatic malformations in the mediastinum manifest as lobular, multicystic tumors that surround and infiltrate adjacent mediastinal structures. Familiarity with the normal radiologic appearance of the retrotracheal space and with the clinical manifestations of diseases that affect the retrotracheal space and adjacent structures can facilitate detection, diagnosis, and management.