Chronic pruritus (CP) is a frequent symptom in the general population; in 8% of all patients, it has a neuropathic origin. CP is of neuropathic origin when nerve fiber damage is responsible for the symptom. The damage can be caused by compression or degeneration of the nerve fibers in the skin or extracutaneous in peripheral nerves or the central nervous system. There are significant differences in the pathogenesis and in the clinical presentation of neuropathic CP. Localized neuropathic CP such as brachioradial pruritus or notalgia paresthetica are due to a circumscribed nerve compression and are often limited on the corresponding dermatome. In contrast, generalized neuropathic CP, as in small fiber neuropathies, may be associated with a systemic or metabolic underlying disease. It is not always easy to establish the diagnosis because a variety of diseases can be responsible for this type of CP. The present study shows an overview of possible diseases, diagnostic tools, and the relevant therapy strategies.