Opioids are some of the most potent analgesics available and their use has been promoted over the last several decades to improve suffering from pain. Unfortunately, with the increased use and access to opioid therapy, significant side effects have surfaced and the death toll caused by opioid overdose has surpassed any other medication, including illegal drugs such as heroin. This observation and the fact that opioid therapy has not met the expectations placed onto it, health care providers and policy makers are seeking alternatives with the intent to avoid opioids. Several nonopioid analgesic strategies have since been studied with variable success, demonstrating that opioid therapy will still play a role in the near future. As health care providers are becoming more aware of the side effects and problems with patient selection, we can assume that a selective approach to opioid therapy will decrease mortality related to this medication class and improve outcomes through the use of better education, compliance monitoring, abuse-deterrent formulations, and a proactive approach to anticipated side effects.