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Fatal poisonings due to fentanyl and its analogues represent a serious and growing threat to public health in North America. This paper looks at why fentanyl was introduced into the illegal drug supply, why it is so deadly and why its use is growing and likely to continue to do so. Many responses to this threat have been proposed, such as harm reduction, decriminalization, increased law enforcement, border control measures, Portuguese-style social control, diplomatic efforts to reduce production in source countries, among others. These approaches are evaluated from feasibility and cost-benefit points of view.