Analgesia for burn patients is often prescribed with opioids at significantly longer and longer doses and durations than analgesic dosing guidelines suggest. However, many patients remain without pain relief. There is also a high risk of developing dependence and opioid use disorder such as hyperalgesia and tolerance. In addition, acute metabolic changes, exacerbated inflammatory cascades, and fluid changes associated with major thermal injuries create significant changes in the volume of distribution and pharmacokinetics of opioids in burn patients. Given these individual and unpredictable variables for each patient and the limited therapeutic windows of these agents, it is evident that pain and opioids require continuous assessment and adjustments for safe and effective pain control in this population, based on dose-response.