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Drug overdose is now the leading cause of injury death in the United States. Most overdose fatalities involve opioids, which include prescription medication, heroin, and illicit fentanyl. Current data reveal that the overdose crisis affects all demographic groups and that overdose rates are now rising most rapidly among African Americans. This publication provides a public health perspective that can be used to mobilize a comprehensive local, state, and national response to the opioid crisis.