Epidemic increases in opioid use in the USA and globally highlight the need for effective adjunctive therapies to opioid-based analgesia. Given the shortcomings of behavioral adjuncts to opioid-based pain treatment, an urgent need exists for pain-related behavioral interventions that resonate with broad patient populations, can be delivered confidentially in any environment, and can incorporate new content automatically. Understanding the potential for automated behavioral therapies like music therapy in modulating the experience of pain may unlock methods to transition patients to lower doses of pharmacologic therapy or provide alternatives to opioids during acute exacerbations of pain. This manuscript describes the neurologic mechanism of action, theoretical basis, and potential applications of personalized music as a smartphone-based mHealth intervention for acute and chronic pain management.