According to historical evidence, the abuse of opium has been reported all over the globe-specifically throughout Eastern nations-since the sixteenth century. Before that, opium had mostly been applied as medication. Reference has been made in traditional Persian medical literature to the method of cultivation, properties, side effects and toxicity. In sixteenth century Iran, during the reign of the Safavids, opium abuse began. It was from then that prominent Persian scholars started to think of solutions to this societal problem. One of the most famous scholars was Imad al-Din Mahmud ibn Mas'ud Shirazi, who composed a book concerning addiction-Afyunieh, a comprehensive book on the topic of opium and all issues of opium. Furthermore, he recommended methods for reducing opium dose as well as substitution with other medications that had a narrower range of side effects, in order to eradicate dependency upon opium and opium-derived materials. This is most likely the first book that comprehensively addressed opium and discussed drug rehabilitation methodology, in traditional Persian medical literature. In this historical review, the authors have introduced the book Afyunieh, which presents methods for treating addiction to and giving up opium; the text comprises a synthesis of the author's opinions, professional experience and references to the work of other famous physicians.