Opioids are one of the cornerstones of acute pain management; however, these medications are not without risk. In light of the opioid epidemic, there has been a focus on the pitfalls and safety concerns of opioid analgesics, such as respiratory depression, tolerance, and gastrointestinal side effects. With these concerns in mind, there has been a push to develop safer opioids. One proposed method uses receptor-biased opioid agonists that preferentially activate the pain-blocking cascade of opioid receptors without activating the β-arrestin pathway. This is important because the β-arrestin pathway is thought to be responsible for the side effect profile of traditional opioids; thus, using receptor-biased agonists could decrease the incidence of respiratory depression, tolerance, and constipation. The current presentation will review the pharmacology of receptor-biased agonists to elucidate whether the current evidence supports these claims and whether there is a role for receptor-biased agonists in pain management.