The war on drugs has failed. It is urgent to find new ways to tackle the problems created not only by drug trafficking but also by the prohibitionist policies and the international regime implemented for decades to fight it. Regulation of the whole value chain (production, trade, and consumption), differentiated according to drug type and informed by scientific evidence, would help reduce harms to consumers and third parties and would deprive organized crime groups and other illegal actors of a large proportion of their profits. The complexity of implementing such regulations can be addressed if there is a clear commitment on the part of the international community to find common solutions to the implementation issues ahead.