Chronic pruritus, or itch lasting greater than 6 weeks, is an increasingly common and debilitating medical problem. Recent studies have unveiled previously unrecognized neuroimmune axes whereby inflammatory cytokines act directly on the nervous system to promote itch. Thus, the emergence of newer targeted biologic therapies has generated the possibility of novel treatment strategies for chronic itch disorders. This article reviews the pathophysiology of multiple chronic itch disorders, including atopic dermatitis, chronic idiopathic pruritus, chronic urticaria, and prurigo nodularis. Furthermore, new and emerging immunomodulatory therapies that will likely alter current treatment paradigms are discussed.