Periventricular enhancement in adults at MRI is a significant finding since it often indicates the presence of an underlying disease requiring prompt medical attention. From a review of patients with periventricular enhancement, the main imaging features based on the underlying infectious or tumoral etiology will be described. The presented differential diagnosis is based on the immune status of the patient, type of enhancement, and response to a trial therapy. In immunocompromised patients, the main considerations are lymphoma and viral ependymitis. The pattern of enhancement is important. The presence of thin linear enhancement suggests a viral etiology (cytomegalovirus or varicella-zoster virus) that can be confirmed at CSF evaluation whereas the presence of nodular enhancement suggests a diagnosis of primary CNS lymphoma that can be confirmed by the presence of lymphomatous cells in the CSF or, more frequently, at stereotactic surgical biopsy performed after failure of response to anti-toxoplasmosis treatment. The presence of band enhancement is less specific and can be seen with viral, lymphomatous and even tuberculous involvement. In immunocompetent patients, a clinical context of infection will suggest bacterial or tuberculous ventriculitis and the presence of cystic lesions will suggest cysticercosis; in the absence of constitutional symptoms, the presence of nodular enhancement will suggest a tumoral process (lymphoma, ependymoma, germ cell tumor, or metastases). Rarely, linear enhancement will be due to sarcoidosis or Whipple's disease.