Small-fiber neuropathy was evaluated just several decades ago but has already been described in the pathogenesis of many diseases, such as early manifestations of diabetes mellitus, immune complications of viral and bacterial infections, and the effects of chemotherapy. This chapter describes the etiology and pathogenesis of small-fiber neuropathy, clinical manifestations, criteria for diagnosis, laboratory and instrumental diagnostics, and principles of therapy. A special emphasis in this chapter is placed on the role of small-fiber neuropathy in the pathogenesis of autoimmune diseases and principles of management of such patients.