Background <p>Ependymal enhancement is an uncommon but diagnostically challenging MRI finding with a wide range of aetiologies.</p> Purpose <p>This pictorial essay presents an algorithmic approach to its differential diagnosis.</p> Results <p>We categorize the ependymal enhancement into three main etiologic groups: infectious disorders, non-infectious inflammatory disorders and tumors, highlighting specific demographic, clinical, and imaging findings that are crucial for diagnosis. We provide two diagnostic algorithms according to the patient’s immune status, since it is paramount in determining the differential diagnosis. For immunosuppressed patients, the workflow focuses on the enhancement pattern (linear, band-like or nodular appearances) and the presence of concomitant intra-axial masses, directing the differential toward entities such as toxoplasmosis or lymphoma. For immunocompetent patients, the diagnostic pathway relies on clinical history and lesion characteristics to distinguish infectious, inflammatory, and neoplastic causes, further refined by the presence or absence of an intra-axial mass.</p> Conclusion <p>These diagnostic algorithms may help neuroradiologists structure the differential diagnosis and improve clinical decision-making.</p>