Objective: Misuse of centrally acting antihistamines is potentially a significant under-recognised issue contributing to problems of abuse and dependence, with the potential to complicate management of other mental disorders. This article considers this problem with the aim of increasing practitioner awareness. Method: This article considers the literature relating to abuse of centrally acting antihistamines and presents a unique case, with features suggesting of psychological and physiological dependence following prolonged misuse of promethazine. Results: Increased understanding of the potential problem of centrally acting antihistamine abuse and consideration of the possibility of a dependence syndrome associated with promethazine. Conclusions: The need for vigilance for abuse potential of promethazine and other centrally acting antihistamines by doctors and pharmacists is emphasised.