Though valuation processes are fundamental to survival of the human species, hedonic dysregulation is at the root of an array of maladies, including addiction, stress, and chronic pain, as evidenced by the allostatic shift in the relative salience of natural reward to drug reward observed among persons with severe substance use disorders. To address this crucial problem, novel interventions are needed to restore hedonic regulatory processes gone awry in persons exhibiting addictive behaviors. This article describes a theoretical rationale and empirical evidence for the effects of one such new intervention, Mindfulness-Oriented Recovery Enhancement (MORE), on top-down and bottom-up mechanisms implicated in cognitive control and hedonic regulation. MORE is innovative and distinct from extant mindfulness-based interventions in that it unites traditional mindfulness meditation with reappraisal and savoring strategies designed to reverse the downward shift in salience of natural reward relative to drug reward, representing a crucial tipping point to disrupt the progression of addiction—a mechanistic target that no other behavioral intervention has been designed to address. Though additional studies are needed, clinical and biobehavioral data from several completed and ongoing trials suggest that MORE may exert salutary effects on addictive behaviors and the neurobiological processes that underpin them.