Melatonin has been proposed as a treatment for tinnitus, especially on the basis of its favourable effects on sleep and its vasoactive and antioxidant properties. However, to our knowledge no attempts of interpretation have been advanced through a detailed analysis of the various specific properties of melatonin possibly cooperating in a coincidental way to relieve tinnitus: among these, its modulatory effect on central nervous system resulting in a protective mechanism against an exaggerated sympathetic drive; its capacity to induce a more steady hemodynamic condition, through a multifactorial and multi-organ activity, resulting in a more regular labyrinthine perfusion; a possible action on the skeletal muscle tending to a reduction of the muscular tone, which could relieve tinnitus of muscular origin deriving from tensor tympani tonic contractions; its possible reported antidepressive effect, which could indirectly act on tinnitus; a direct regulation of inner ear immunity as proposed in literature when melatonin was reported to be present in the inner ear. All these observations seem to indicate melatonin as a tool deserving a greater attention than other antioxidants in the attempt of relieving tinnitus, justifying its application from a more precise rationale based on a series of physio-pathological aspects.