Today, skin biopsies can play an important role in the diagnosis of peripheral nerve disorders and have yielded another diagnostic tool for the neurologist. One of the commonly reported neuropathologic abnormalities observed in skin biopsies is a reduction of epidermal nerve density. Analyzing the changes in the morphology and density of epidermal nerves is of immense diagnostic and prognostic value in peripheral neuropathies. These changes also provide an assessment of disease progression and of tissue responses to regenerative treatments. Combined with immunohistochemical studies, newly evolved skin biopsy and epidermal count techniques have the potential to provide significant information about the pathogenesis of many peripheral nervous system diseases. They have great potential for impacts on both research and clinical approaches to treatment. Evolution of a standardized and validated counting methodology and significant advances in procuring skin biopsies have opened up a wide spectrum of applications that make the technology easy to apply in practice. The application of this technology may lead to early detection of many common peripheral nerve diseases and an enhanced understanding of disease onset and progression. In this article we review the state of current research and clinical practice in the use of skin biopsies and epidermal nerve densities.