This work evaluates trials on drug treatment of tinnitus. Tinnitus is a subjective complaint and there are no objective outcome measures. The rationale of treating tinnitus is based on two major therapeutic models: 1) cochlear origin of tinnitus in that tinnitus is alleviated by cochlear mechanisms reducing the cytotoxicity induced by the metabolic stress, influencing neural transmission and restoring the cochlear homeostasis. 2) central origin of tinnitus that involves similar mechanisms to neuropathic pain. In controlled studies there are no convincing results that any treatment will be beneficial for tinnitus. There are some exceptions with drugs that antagonize neurotransmission in glutaminergic receptors, and also possibly melatonin when sleep disorders are associated with tinnitus. The central neurotransmitter agonists and antagonists seem not to be effective. Finally, novel nano-technological advances in targeted drug carrier technology that can administer growth factors and gene machinery may be useful in future treatment of tinnitus.