Itch is propagated by complex mechanisms located both peripherally and within the central nervous system. For decades, novel treatments of itch have been slow to emerge, with the majority of focus on antagonism of histamine. Recently, with a new understanding of the pathophysiology of itch transmission, new treatment strategies have been elucidated. Opiate receptor antagonists, antidepressants, antiepileptics, and thalidomide are currently available therapeutic options that have benefited many patients with variegated sources of itch. In addition, research focused on the neuromediators of itch transmission has led to the development of novel targets for itch reduction and great potential for future therapies.