The pleura is a thin, smooth, soft-tissue structure that lines the pleural cavity and separates the lungs from the chest wall, consisting of the visceral and parietal pleurae and physiologic pleural fluid. There is a broad spectrum of normal variations and abnormalities in the pleura, including pneumothorax, pleural effusion, and pleural thickening. Pneumothorax is associated with pulmonary diseases and is caused by iatrogenic or traumatic factors. Chest radiography and US help detect pneumothorax with various signs, and CT can also help assess the causes. Pleural effusion occurs in a wide spectrum of diseases, such as heart failure, cirrhosis, asbestos-related diseases, infections, chylothorax, and malignancies. Chest US allows detection of a small pleural effusion and evaluation of echogenicity or septa in pleural effusion. Pleural thickening may manifest as unilateral or bilateral and as focal, multifocal, or diffuse. Various diseases can demonstrate pleural thickening, such as asbestos-related diseases, neoplasms, and systemic diseases. CT, MRI, and fluorodeoxyglucose (FDG) PET/CT can help differentiate between benign and malignant lesions. Knowledge of these features can aid radiologists in suggesting diagnoses and recommending further examinations with other imaging modalities. The authors provide a comprehensive review of the clinical and multimodality imaging findings of pleural diseases and their differential diagnoses. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.