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Opioid use has increased significantly over the past ten years and so has the incidence of reportable adverse events, such as respiratory depression and/or arrest. It is important for nurses to understand and know how to assess patients for risk factors for respiratory depression secondary to opioid therapy. This paper presents the pharmacodynamics of opioids, the risk factors for excessive respiratory depression, recommendations for identifying patients at high risk, and interventions to prevent adverse effects. After reading this paper, nurses will have the knowledge to provide safe administration of opioid medications for the management of acute pain.