Fentanyl is a highly potent opioid developed for pain management (it is significantly more potent than heroin or morphine). Fentanyl was first approved for medical use in America in 1968 and has become a widely prescribed drug. However, fentanyl has become a major contributor to the epidemic of opioid drug overdose deaths in the United States; most research suggests that as of 2018, fentanyl was responsible for the majority of drug overdose deaths in America (surpassing heroin). Because of its potency, a relatively small amount of fentanyl can result in overdose, and higher doses of lifesaving drugs such as Naloxone may be needed to counteract an overdose.

Prescription opioids were initially not recommended for chronic pain and were intended to manage acute pain for individuals suffering from terminal illness; however, in the 1980s and 1990s, advocacy and promotional efforts from pharmaceutical companies (some of whom made misleading claims that individuals could not become addicted to opioids) led to opioids being prescribed more widely in the United States, including in response to chronic, non-life-threatening conditions. Opioids are now known to be highly addictive, and this characteristic plays a significant role in dependency and the risks of overdose. Consistent use of opioids can contribute to increased tolerance to the drugs, forcing users to take higher and higher doses to manage their pain, and thus raising overdose risks.