The etiology of tinnitus combines hereditary and environmental factors. To help develop optimal therapies for tinnitus, it is necessary to characterize the genetic contributors to the pathophysiology and to design treatments at the level of the gene. Inner ear gene therapy involves delivery of genes into the vestibular or auditory portions of the inner ear for preventive or reparative therapies at the level of the sensory epithelium or the eighth nerve neurons. BDNF and GDNF are among the neurotrophic factors shown to be overexpressed with gene therapy and to protect the inner ear against trauma. Combined treatment with Ad.GDNF and electrical stimulation provided enhanced preservation of denervated spiral ganglion neurons. The use of viral vectors for gene therapy may involve side effects, including immune response to the viral proteins. Treatment with immunosuppressive medications can reduce the negative consequences of adenovirus-mediated gene therapy.