Advances in neuroscience are changing how mental health issues such as addiction are understood and addressed as a brain disease. Although a brain disease model legitimizes addiction as a medical condition, it promotes neuro-essentialist thinking and categorical ideas of responsibility and free choice, and undermines the complexity involved in its emergence. We propose a “biopsychosocial systems” model where psychosocial factors complement and interact with neurogenetics. A systems approach addresses the complexity of addiction and approaches free choice and moral responsibility within (...) the biological, lived experience and sociohistorical context of the individual. We examine heroin-assisted treatment as an applied case example within our framework. We conclude with a discussion of the model and its implications for drug policy, research, addiction health care systems and delivery, and treatment of substance use problems. (shrink)