Purpose of Review <p>Tens of millions of individuals worldwide suffer from chronic pain that drives significant emotional and motivational tolls with few safe treatments. This problem is compounded by the fact that several legal and illicit substances serve as powerful pain relievers. The antinociceptive efficacy of these agents (including alcohol, opioids, and cannabis) can drive negative reinforcement processes whereby analgesics are used to self-medicate somatic and emotional dimensions of pain that may be associated with the progression to substance use disorders (SUDs). This review communicates recent translational research findings and conceptualizations at the biobehavioral intersection of pain and SUD.</p> Recent Findings <p>Chronic pain engages higher nociceptive circuitry within key cortical and subcortical brain areas. As these regions are critically involved in the manifestation of numerous emotions and affective disorders, there is currently a focus on translational research to identify specific points of intersection among disorders of pain-related emotional dysregulation. Another underappreciated domain of chronic pain is the cognitive dysfunction that it engenders, as executive function deficits are a hallmark of SUD and may represent another key construct whereby pain drives relapse propensity.</p> Summary <p>Future therapeutic approaches targeting pain and SUD should ensure that the emotional and cognitive elements of pain are fully appreciated.</p>