Drug policy in the American hemisphere is in flux. After decades whereby a prohibitionist regime reigned supreme and proposing alternatives was taboo, several countries have begun to reconsider policy, particularly in the case of marijuana. International law has been instrumental in building the legal and institutional regime of prohibition, and it has remained largely impervious to critiques of its disastrous consequences. Indeed, when it comes to drug law and policy, international law has been part of the problem. Nevertheless, countries in the Americas have begun to adopt innovative strategies that also embrace international obligations. In this essay, I examine the failures of the law and order paradigm behind prohibition. I then analyze legal reforms in the Americas as motivated by three different perspectives: 1) human rights, 2) public health and 3) political economy. Each one offers a powerful challenge to prohibition but relies on different assumptions and offers different transformative potential.