It has been over half a century since the landmark Single Convention on Narcotic Drugs was adopted, for the first time unifying international drug policy under a single treaty aimed at limiting use, manufacture, trade, possession, and trafficking of opiates, cannabis, and other narcotics. Since then, other international drug policy measures have been adopted, largely emphasizing enforcement-based approaches to reducing drug supply and use. Recently, in response to concerns that the historic focus on criminalization and enforcement has had limited effectiveness, international drug policies have begun to undergo a paradigm shift as countries seek to enact their own reforms to partially depenalize or deregulate personal drug use and possession. This includes Mexico, which in 2009 enacted national drug policy reform partially decriminalizing possession of small quantities of narcotics for personal consumption while also requiring drug treatment for repeat offenders. As countries move forward with their own reform models, critical assessment of their legal compatibility and effectiveness is necessary. In this debate piece, we conduct a critical assessment of the compatibility of Mexico’s reform policy to the international drug policy regime and describe its role in the current evolving drug policy environment. We argue that Mexico’s reform is consistent with flexibilities allowed under international drug treaty instruments and related commentaries. We also advocate that drug policy reforms and future governance efforts should be based on empirical evidence, emphasize harm reduction practices, and integrate evidence-based evaluation and implementation of drug reform measures.