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Mitigating harm is not easy: drug use patterns are shifting (as illustrated by the rise of synthetic opioids) and vary widely between urban and rural settings and among marginalised populations. Decriminalisation works, but not in isolation; and although it does not mean removing law enforcement from the complex environment of drug use, it does require health professionals, and not the criminal justice system, to be the first responders to this public health crisis. Evidence to show that criminalisation has failed is overwhelming. Bold and comprehensive reforms are needed to pursue health-oriented, rights-based drug decriminalisation policies. What more will it take for policy makers to listen?