Imaging plays a pivotal role in diagnosing, managing, and monitoring mediastinal and hilar diseases, which encompass a diverse range of benign, malignant, infectious, and inflammatory conditions. These diseases are localized within the complex mediastinum, which is anatomically divided into prevascular, visceral, and paravertebral compartments. Each compartment is associated with specific pathologies, enabling imaging-based localization to narrow differential diagnoses and guide clinical management. This review explores the imaging features, clinical presentations, and implications for the eight most common mediastinal and hilar diseases: mediastinal and hilar lymphadenopathy, thymoma, bronchogenic cyst, neurogenic tumor, substernal thyroid goiter, lymphoma, teratoma, and sarcoidosis. Computed tomography (CT) and magnetic resonance imaging (MRI) are the primary modalities for characterizing these conditions, while positron emission tomography (PET) aids in assessing metabolic activity, particularly in malignancies and active inflammation. Key imaging features such as location, attenuation, calcifications, enhancement patterns, and metabolic activity inform differential diagnoses and management decisions. Clinical implications include determining disease extent, staging malignancies, planning surgical interventions, and guiding biopsies. Understanding the characteristic imaging patterns and their clinical correlations is essential for radiologists and referring physicians to optimize patient care in these complex and often overlapping conditions. This review provides practical insights and imaging pearls to improve diagnostic accuracy and treatment planning for these diseases.