We seek to optimise mental health frameworks and address substance use through culturally informed models of care. Our researchers have undertaken some of the first robust, Indigenous-focused studies aiming to understand the scale of the mental health burden in Aboriginal and Torres Strait Islander communities, and have pioneered community-led and co-designed initiatives such as the I-ASIST suicide first aid training program. We investigate patterns of drug dependence and its links to infectious disease, detention and imprisonment among Aboriginal and Torres Strait Islander peoples, and use this knowledge to develop harm reduction and treatment programs.