Regardless of specialty or practice environment, most prescribers will encounter patients with substance misuse in their practice. Data from the Substance Abuse and Mental Health Administration’s 2021 National Survey on Drug Use and Health suggests that almost 60% of people in the United States aged 12 or older used tobacco, alcohol, or an illicit drug within the past month. Another study showed that more than 46 million people aged 12 or older (16.5% of US residents) met the applicable DSM-5 criteria for having a substance use disorder involving alcohol or drugs in the past year, but 94% of them did not receive any treatment. This learning activity focuses on 4 areas of risk a provider may encounter in clinical practice: (1) safe monitoring strategies for patients receiving buprenorphine, (2) naloxone and post-overdose monitoring, (3) benzodiazepine toxicity, and (4) Non-opioid pain management treatment options.