The article reviews the extensive literature on the relationship between chronic stress and addiction, highlighting its role in increasing vulnerability to addiction and relapse. It discusses the neurobiological mechanisms underlying this association, including the effects of stress on the corticotropin-releasing factor (CRF) system, the hypothalamic-pituitary-adrenal (HPA) axis, and the noradrenergic system. The article also explores how these alterations impact the corticostriatal-limbic motivational, learning, and adaptation systems, particularly the mesolimbic dopamine, glutamate, and gamma-aminobutyric acid (GABA) pathways. Additionally, it examines the impact of chronic drug use on these stress and motivational systems, emphasizing the role of these adaptations in stress regulation, impulse control, and compulsive drug seeking. The review concludes by identifying research gaps and suggesting future directions for understanding and addressing the stress-related risk of addiction, with a focus on developing new prevention and treatment strategies.The article reviews the extensive literature on the relationship between chronic stress and addiction, highlighting its role in increasing vulnerability to addiction and relapse. It discusses the neurobiological mechanisms underlying this association, including the effects of stress on the corticotropin-releasing factor (CRF) system, the hypothalamic-pituitary-adrenal (HPA) axis, and the noradrenergic system. The article also explores how these alterations impact the corticostriatal-limbic motivational, learning, and adaptation systems, particularly the mesolimbic dopamine, glutamate, and gamma-aminobutyric acid (GABA) pathways. Additionally, it examines the impact of chronic drug use on these stress and motivational systems, emphasizing the role of these adaptations in stress regulation, impulse control, and compulsive drug seeking. The review concludes by identifying research gaps and suggesting future directions for understanding and addressing the stress-related risk of addiction, with a focus on developing new prevention and treatment strategies.