Substance addiction is a biopsychosocial challenge in living characterized by impairment in three primary areas of brain-behavior functioning: motivation/reward system; learning and memory processing; and impulsivity and behavioral control. The neuroscience literature has begun to identify the disrupted neural pathways and functional impairments that may lead to reduced emotional competence and diminished decision-making ability. High cortisol levels are associated with greater risk for substance use disorders in depressed adolescents, specifically when experiencing other significant stressors, suggesting that substances may be used to modify hypothalamic-pituitary-adrenal (HPA) activity level. The neuroscience literature has dramatically influenced innovations in addiction treatment. Three of these innovation areas are highlighted: community engagement models of addiction and recovery; dual processing practice models; and an integrated neurosystems approach. The World Health Organization calls for government policies that support not only neurobiological research on addictions, but that also “link” neuroscience and social science research within the field of addictions.