This review paper was one of seven commissioned by the Australian Government Department of Health and Aging as part of an inter-departmental review of Indigenous primary health care. The review put a primary health care approach to substance misuse into the context of patterns of alcohol and other drug use, the health harms associated with substance misuse, the underlying causes of higher levels of use in Indigenous populations, and the broader range of Indigenous substance misuse interventions. It made a number of recommendations in the areas of: expansion of, and support for, the human resource base; workforce development; program development; primary prevention and early intervention; and integration of services and activities. Among others, an outcome of this and the associated reviews was an increase in funding for primary health care services.