Despite the predominance of itch as a leading and distressing symptom in most of the dermatological and several systemic diseases, there is relatively little progress in understanding its pathophysiology. This is most likely the main reason for the limited number of satisfactory anti-itch treatments and the fact that even today various therapies have empirical but not evidence-based character. There are no specific antipruritic drugs on the market, but there are a high number of case reports and experimental investigations describing medications with antipruritic potency. It is therefore the aim of this article to briefly review the major systemic antipruritic drugs and give a short overview on the different types of pruritus and their possible systemic therapy.