Chronic itch is a distressing symptom that is often recalcitrant to standard anti-itch therapies. Distinct from acute itch in its duration and response to common treatments, chronic itch is a frustrating symptom for patients and their physicians alike. However, emerging research into the underlying neuropathophysiology of chronic itch has provided insights into the biochemical pathways that are responsible for itch transmission. By elucidating the neural pathways that belie this difficult symptom, recent advances in pharmacotherapy have been made possible. In this article, we will outline a few of the mediators responsible for itch transmission and discuss some of the current and future drug therapies that may offer relief to chronic itch sufferers.