Substance misuse is a critical and costly public health problem in the United States. Data as of 2016 show 11,517 cases of opioid analgesic misuse, with the majority (6924 cases) related to hydrocodone misuse. Substance misuse impacts our society significantly with high costs related to healthcare, crime, and lost productivity. Opioid analgesic pain relievers are one of the most prescribed classes of medications and are among the most common drugs related to misuse. Increases in emergency department visits of over 200% have been associated with a dramatic surge in written prescriptions for opioid pain relievers. Mortality with opioid misuse has increased dramatically, with 2016 statistics demonstrating 42,249 deaths from any opioid; 15,469 heroin-related deaths; 14,487 deaths related to natural and semi-synthetic prescription agents; 19,413 deaths caused by mainly illicit use of synthetics (mostly fentanyl); and 3373 deaths related to methadone use. Per the Centers for Disease Control and Prevention (CDC), 3 of 5 drug overdoses are from an opioid, such as heroin, morphine, and prescription pain relievers. In addition, the expenses associated with drug use disorders are comparable to the costs of other chronic diseases, such as diabetes. Policymakers, criminal justice officials, and healthcare providers consider illicit drug and opioid misuse a national epidemic that must be addressed more strongly to improve pain management in the United States, optimize patient outcomes, and decrease unlawful drug use for pain relief.