The opioid epidemic in the United States has exposed the need for providers to limit opioid dispensing and identify at-risk patients prior to prescribing opioids. With pharmacogenomic testing, clinicians can analyze hundreds of medications-including commonly prescribed opioids-against genetic results to understand and predict risk and response. Moreover, knowledge of genotypic variants and altered function can help decrease trial and error prescribing, identify patients at-risk for adverse drug events, and improve pain control. This patient case demonstrates how pharmacogenomic test results identified drug-gene interactions and provided insight about a patient's inadequate opioid therapy response. With pharmacogenomic information, the patient's healthcare team discontinued opioid therapy and selected a more appropriate regimen for osteoarthritis (ie, celecoxib), resulting in improved pain control and quality of life.