Neuropathy is a common, untreatable complication of type 1 and type 2 diabetes. In animal models peptide neurotrophic factors can be used to protect against the development of neuropathy, but the combination of short half-life and off-target effects of these potent pleiotropic peptides has limited translation to human therapy. Gene transfer is a promising strategy that may circumvent these limitations. In this article, we review the basic methods of gene transfer and the -preclinical data in rodent models that support the use of this approach in the treatment of diabetic neuropathy. The path to clinical applications and potential pitfalls in developing gene therapy for the treatment of diabetic neuropathy are considered.