What conduct can and cannot legitimately be prohibited through the criminal law? Few topics powerfully illustrate the issues raised by this question including the criminalisation of drugs. In this paper, we are examining the legitimacy of drug criminalisation by critically examining the arguments both for and against it. In doing so, we will confront the fundamental question of what can serve as a valid justification for criminalisation – as well as how criminalisation can often turn out to be ineffective, counter-productive, or even actively harmful. We will also discuss how the criminal law’s approach to drugs is changing in some jurisdictions. Under traditional models of drug criminalisation, it is criminal to produce, import, export, supply, and/or possess any of a list of controlled substances: for example, heroin, cannabis, or cocaine. In recent years, however, this approach has increasingly been criticised for its inability to tackle the growing problem of new psychoactive substances, or “legal highs”. This new threat has led some jurisdictions to develop new legislative models. In the UK, for example, it is now criminal to produce or supply (but not merely to possess) anything that meets the definition of a “psychoactive substance” – a definition that seems to catch many entirely harmless substances, as well as substances that mimic controlled drugs. Are such “catch-all” prohibitions a legitimate form of criminalisation?