Amyloidosis is a rare diverse condition caused by the pathologic extracellular deposition of abnormal insoluble proteins throughout the body. It may exist as a primary disease or, more commonly, may be secondary to a wide variety of pathologic processes ranging from chronic infection or inflammation to malignancy. Hereditary forms also exist. On the basis of the structure of the protein deposits, more than two dozen subtypes of amyloidosis have been described. A single organ or multiple organ systems may be affected. The radiologic manifestations of amyloidosis are varied and often nonspecific, making amyloidosis a diagnostic challenge for the radiologist. In the chest, the lungs, mediastinum, pleura, and heart may be involved. Lung involvement may manifest as diffuse reticulonodular interstitial thickening, consolidations, or solitary or multiple parenchymal nodules that may calcify, cavitate, and slowly enlarge. Pleural involvement most commonly manifests as pleural effusions. Tracheobronchial involvement may exhibit concentric airway thickening, mural and intraluminal nodules, submucosal calcification, and airway obstruction. Mediastinal and hilar lymph nodes may enlarge and frequently calcify. At cardiac magnetic resonance (MR) imaging, the left ventricular wall is typically thickened, with associated diastolic dysfunction. Delayed contrast material–enhanced cardiac MR imaging typically shows global transmural or subendocardial enhancement. The pathophysiology, classification, treatment, and prognosis of amyloidosis are reviewed, followed by case examples of the appearance of thoracic and cardiac amyloidosis on chest radiographs, computed tomographic (CT) images, and cardiac MR images.