A major impediment to any nation abandoning the policy of drug prohibition has been the fact that international drug treaties to which the majority of United Nations (UN) member states are signatory prohibit the non-medical use of amphetamines, cannabis, cocaine and heroin. The future of these treaties is now uncertain because of decisions by Uruguay, eight US states and Canada to legalize cannabis use. This paper: (1) provides a brief account of the international drug control treaties; (2) outlines the major criticisms of the treaties; (3) analyses critically proposals for treaty reform; and (4) provides a personal view on policies that nation states could adopt to minimize the harms from the use of cannabis, party drugs and hallucinogens, opioids, stimulants and new psychoactive substances. It is argued that: a major risk of cannabis legalization in the United States is promotion of heavy use and increased harm by a weakly regulated industry; some cautious national experiments with the regulation of party drugs and hallucinogens would be informative; a strong case remains for prohibiting the nonmedical use of opioids while mitigating the adverse effects that this policy has on opioid-dependent people; stimulant legalization will probably increase problem use but prohibition is difficult to enforce, highlighting the urgency of finding better ways to reduce demand for these drugs and respond to problem users; and that it is unclear what the best approach is to reducing possible harms that may arise from the use of new psychoactive substances.