Recent years have seen a growing unwillingness among increasing numbers of States parties to fully adhere to a strictly prohibitionist reading of the UN drug control conventions; the 1961 Single Convention on Narcotic Drugs (as amended by the 1972 Protocol), the 1971 Convention on Psychotropic Substances; and the 1988 Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. Such behaviour has been driven by a belief that non-punitive and pragmatic health oriented domestic policy approaches that are in line with fundamental human rights standards better address the complexities surrounding illicit drug use than the zero-tolerance approach privileged by the present international treaties. Those treaties were negotiated and adopted in an era when both the illicit market and understanding of its operation bore little resemblance to those of today. Since this stance runs counter to the rigid interpretative positions held by some parts of the UN drug control apparatus, and many other States Parties, tensions within the international treaty system, or what has usefully been called the global drug prohibition regime, are currently pronounced. What can be called ‘soft defecting’ states, those choosing to deviate from the prohibitive ethos of the conventions whilst remaining within what they deem to be the confines of their treaty commitments, are regularly criticized by the International Narcotics Control Board (INCB) for engagement, in some cases at a subnational level, with a range of tolerant policy approaches. Prominent among these are harm reduction interventions aiming to reduce the link between injecting drug use and HIV/AIDS (particularly drug consumption rooms/safe injection facilities), medical marijuana schemes and the ‘decriminalization’ of drug possession for personal use. Despite the positions of the Board, the detailed and robust legal justifications put forward by many states demonstrate that the policy choices are defensible within the boundaries of the existing treaty framework. Moreover, they are further justified, and in some cases required, by national constitutional guarantees and concurrent obligations in international law. That national constitutional principles should operate as the locus for determining the appropriateness of certain policies (such as the criminalisation of personal possession of illicit substances) is specifically written into the drug control conventions. Although revealing their considerable flexibility, the process of soft defection also inevitably highlights the limited plasticity of the conventions – they can only bend so far. The very act of justifying the legality of various policy options relative to the treaty framework emphasises an inescapable fact. Should they wish to do so, states already pushing at the limits of the regime would only be able to expand further national policy space, particularly in relation to production and supply, via an alteration in their relationship to the conventions and the prohibitive norm at the regime’s core. Within such a context, growing and much needed attention is being devoted to the legal technicalities of treaty revision. There remains, however, a deficiency of analysis and discussion of the political and geopolitical practicalities of moving beyond the prohibitive confines of the current treaty framework. This discussion paper aims to go some way to fill this space. Mindful of the recent experiences of the Plurinational State of Bolivia in the first formal challenge to the prohibitive norm at the heart of the regime, it focuses specifically on the possible benefits and dilemmas of the formation and operation of a like-minded group (LMG), or groups, of revisionist nations. The paper suggests that, while substantive changes in the structure of international regimes in general is not uncommon, the varied nature of dissatisfaction with different aspects of the current drug control regime, the relatively few States parties openly expressing such dissatisfaction, and the character of drug policy itself combine to make the issue more problematic than it might be in other areas of multilateral cooperation. As will be discussed, the history of the issue area and the current mechanisms of regime compliance point to the use of an LMG approach to expand domestic policy freedom via some form of treaty revision. Yet, the inter-related issues of specific and often shifting national interest are likely to make such a process complex and multifaceted. Key Points: Despite interpretative tensions around some policy approaches, inherent flexibility within the UN drug control conventions allows members of the drug control regime some policy space at the national level. Should they wish to do so, however, states already pushing at the limits of the regime would only be able to expand further national policy space via an alteration in their relationship to the UN drug control conventions and the prohibitive norm at the regime’s core. Mindful of the political and procedural dynamics of the regime, the formation and operation of a group, or groups, of like-minded nations appear to be the most logical and promising approach for some form of treaty revision. The varied nature of dissatisfaction with the prohibitive ethos of the regime combines with the character of drug policy to generate dilemmas for the like-minded group approach. Within the current environment it is plausible to suggest groupings around traditional and religious uses, cannabis regulation, technical issues and system-wide coherence. The centenary of the regime is an opportune moment to consider some form of treaty revision and the formation of like-minded groups to that end.