Itch is a noxious sensation that disturbs work and play while awake and prevents rest and rejuvenation during sleep. Itch accompanies many skin diseases from psoriasis to urticaria to various types of eczema and to ectoparasitosis such as scabies. Although the pathogenesis of itch is not well understood, it has neurophysiological similarities to and differences from pain. Recent investigations have defined both indirect and direct roles for cytokines in itch. Indirectly, cytokines activate cells of the immune system and resident cells in skin to release mediators that communicate with sensory nerves regulating neurogenic inflammation, pain, and/or itch. Certain cells, for example mast cells and eosinophils, communicate with sensory nerves during inflammation via mediators, including histamine, tryptase, and prostanoids, that induce pruritus. Information about how other immune cells, particularly T cells, communicate with nerves to influence neurogenic inflammation, pain, and pruritus is limited. Therapies directed at cytokines that are involved in proinflammatory immune responses, for example, IL-4, IL-13 (dupilumab in atopic dermatitis), IL-17 and IL-22 (secukinumab, ixekizumab, brodalumab in psoriasis), reduce the symptoms of itch. Emerging evidence indicates that cytokines, including chemokines, involved in inflammation, for example, IL-1, IL-8, IL-10, monocyte chemoattractant protein (MCP), CCL2, CCL4, CCL5, macrophage inflammatory protein 1 alpha (MIP1α), directly communicate with sensory nerves via activation of high-affinity receptors. Recent studies have shown that two members of the IL-6 cytokine family, IL-31 and oncostatin M (OSM), are important in T-cell-induced neuronal communication. IL-31 receptors are constitutively expressed on the surface of keratinocytes, eosinophils, and small diameter neurons. Nemolizumab (CIM331), a humanized monoclonal antibody against IL-31 receptor A, inhibits IL-31 signaling with improvement in pruritus when administered to patients with atopic dermatitis supporting the role of IL-31 in the pathogenesis of pruritus in this disease.