There exists a multitude of medical conditions that cause intractable itch, or pruritus. The successful management of this symptom depends explicitly on establishing the underlying cause. Studies have shown that drugs not traditionally used in the treatment of cutaneous disorders, such as opiate receptor antagonists, antidepressants, and antiepileptics, can provide symptomatic relief of intractable itch. These novel antipruritic agents will be explored in this review.