Immune-mediated inner ear disease (IMIED) is a syndrome that includes the subacute onset of sensorineural hearing loss, often accompanied by vertigo and tinnitus. This constellation of symptoms may occur as a primary disorder in which no other organ involvement is evident, or it may complicate certain systemic conditions, including Wegener’s granulomatosis, Cogan’s syndrome, polyarteritis nodosa, and systemic lupus erythematosus. The precise disease mechanisms remain undefined, largely because of the difficulty obtaining relevant tissue specimens in untreated patients. However, if treated promptly with aggressive immunosuppression, the devastating sequelae of IMIED may be avoided. In this article, we review the pathophysiology, clinical evaluation, diagnostic testing, and therapy of IMIED.