ABSTRACT: A patient's psychological condition can substantially affect the presence and severity of pruritus, a phenomenon thought to be mediated by the central nervous system's (CNS) opioid neurotransmitter system. Specific psychodermatologic disorders associated with psychogenic pruritus, including depression, anxiety, chronic tactile hallucinations, delusions of parasitosis, neurotic excoriations, and other cutaneous compulsions are likely controlled by this pathway. Therefore, in treating these conditions, medications specifically directed at the CNS can be the most effective therapies, whereas topical and supportive therapy may be important adjuncts in targeting the associated pruritus. Furthermore, the impact of an understanding clinician and a good physician–patient relationship cannot be underestimated in determining ultimate prognosis. This review will begin by discussing the relationship between the psyche and pruritus as well as the opioid neurotransmitter system. Following this, several disorders characterized by psychogenic pruritus will be described, and CNS-specific and adjunctive topical and supportive therapies for these conditions will be detailed.