Skin biopsy is a safe, minimally invasive, painless and cheap tool for providing diagnostic information on small nerve fibers, which are invisible to routine neurophysiological tests. Biopsy can be performed in hairy skin to investigate unmyelinated and thinly myelinated fibers and in glabrous skin to examine large myelinated fibers. Morphometric analysis of skin nerves is readily accomplished through the use of immunohistochemical techniques, and has proved to be reliable, reproducible and unaffected by the severity of neuropathy. One further advantage of skin biopsy over conventional nerve biopsy is that it allows somatic nerve fibers to be distinguished from autonomic nerve fibers. Morphological changes, axonal degeneration and abnormal regeneration occur in cutaneous nerves very early in the course of peripheral neuropathies, making skin biopsy a promising tool for investigating the progression of neuropathy and the effect of neuroprotective treatments in clinical practice and trials. This article reviews the techniques that are used to investigate the innervation of human skin, the possible uses of skin biopsy in diagnosing and monitoring peripheral neuropathies, and correlations between skin biopsy findings and those of other diagnostic methods.