Adherence to pain self-management strategies is associated with favorable psychobehavioral outcomes among individuals with chronic pain. Substantive adherence to treatments teaching these adaptive skills proves challenging, resulting in poor individual and societal outcomes. Evidence demonstrates motivation for behavior change as a key predictor of treatment adherence. Despite behavioral techniques that target motivation, however, nonadherence persists as a barrier to positive clinical outcomes in chronic pain. Understanding the neurobiological mechanisms underlying treatment motivation might highlight novel avenues for augmentative therapies. The purpose of this review is to present theory and evidence that the mesocorticolimbic system (i.e., brain circuitry associated with reward processing and motivation) contributes to treatment motivation among chronic pain patients, ultimately influencing adherence. We review evidence for motivation as a key adherence determinant, detail neuroimaging findings relating mesocorticolimbic circuitry and motivation, and discuss data supporting mesocorticolimbic dysfunction among chronic pain patients. We propose a neurobehavioral model for adherence to pain self-management interventions, listing testable hypotheses. Finally, we discuss potential research and intervention implications from the proposed model.