There has been a great deal of scholarly activity devoted to the burgeoning rates of prescription opioid misuse, abuse, and related fatalities. Practice guidelines have been developed to influence opioid prescribing in the outpatient setting. Nonopioid perioperative protocols have been encouraged to reduce unnecessary exposure to opioids to potentially vulnerable patients. Approximately 8% to 10% of patients with chronic pain who are prescribed opioids go on to develop opioid use disorders. While this is not an inconsequential number of patients, the focus on opioids has overshadowed other substances of abuse that can be equally as harmful, impacting an individual’s quality of life. This presentation will provide an update on the current science and literature of opioid abuse and opioid use disorder in patients with chronic pain and will discuss the prevalence, risk assessment, and mitigation strategies of other often abused substances in this patient population, including alcohol, nicotine, and cannabis.