Prescription opioid analgesics are an essential treatment option for patients with moderate to severe pain. Over the last decade the increased medical use of these agents has contributed to a public health epidemic of abuse, addiction, and overdose-related deaths. These medications remain mainstays in both primary care and pain management practices. As palliative services are incorporated at earlier stages of the disease process and the number of individuals with chronic illness increases, palliative care specialists may encounter an increasing number of patients with opioid abuse and addiction problems. Extended-release (ER) and long-acting (LA) opioid formulations are administered to patients with moderate to severe chronic pain requiring around-the-clock analgesia. Given the large quantity of active ingredient contained within some dosage strengths, this medication class is associated with serious risks when taken improperly. In response to growing reports of abuse and overdose deaths, the US Food and Drug Administration (FDA) announced the need for a risk mitigation strategy for the entire class of medication. The class-wide Risk Evaluation and Mitigation Strategy (REMS) for ER/LA opioids will emphasize prescriber training and patient education to ensure that the therapeutic benefits outweigh the risks of addiction, unintentional overdose, and death. As primary care, pain management, and palliative care clinicians often encounter patients who require ER/LA opioids, an understanding of the suggested requirements and potential impact of this regulation is essential.