Substance use among women is a major public health concern. This review article takes a developmental-relational approach to examine processes through which early relational trauma and violence in relationships may lead to substance use. We examine how early exposure to violence in relationships can impact neurological development, specifically through interference with physiological mechanisms (e.g., the hypothalamic-pituitary-adrenal axis), brain structure and functioning (e.g., the hippocampus and prefrontal cortex), and neuropsychological development (e.g., executive functioning and emotion regulation) across the lifespan. Further, we discuss the impact of exposure to violence on the development of relational capacity, including attachment, internal working models, and subsequent interpersonal relationships across the lifespan, and how these developmental pathways can lead to continued problematic substance use in women.