The backbone of the United Nations drug control system consists of three UN Drug Conventions. The prohibition of potentially harmful substances has its origin in the desire to protect human well-being. However, the way in which the global regime was set up decades ago and the escalation of repression it has brought about since, has been an historical mistake increasing rather than diminishing the problems. There is no point now in dreaming about how the world might have looked without it, or deluding ourselves that all the problems could be solved by scrapping the conventions. The challenge is to create the political space which would allow a reform process to move ahead. A process guided by pragmatism, open-mindedness and evaluation of practices on the basis of costs and benefits; providing leeway for experimentation and freedom to challenge the wisdom of the existing conventions.