In this paper, I present and criticize several historical arguments in favour of prohibition and criminalization of illicit psychoactive substances. I consider several versions of Charles Brent’s argument from drug harms and an argument from addiction based on Kantian view on autonomy. My criticism will mainly rely on empirical evidence on drugs, drug use, and addiction. I think that in light of this evidence, all of the arguments lose their cogency or can be refuted altogether. Moreover, the evidence reveals an inconsistency in the international drug law framework. In conclusion, I therefore provide a general argument challenging the legitimacy of the existing distinction between licit and illicit drugs based on the inconsistency.