BACKGROUND: In trying to help Aboriginal and Torres Strait Islander (Indigenous) individuals or communities to stop smoking or reduce the harms from alcohol, it is important to be aware of the strong biological basis of the drive to return to nicotine or alcohol. METHODS: In this paper we briefly describe the social and neurobiological factors that drive a dependent smoker or drinker to keep using. We set out the current range of pharmacological treatments for dependence, their role in assisting a person to either stop using or avoid relapse, and we discuss issues relating to their use in Aboriginal Australians. CONCLUDING COMMENTS: There is a firm evidence base for the use of pharmacological treatments for nicotine or alcohol dependence, particularly in severe dependence or when counselling or non-pharmacological approaches have failed. Indigenous Australians should be able to access the full range of approaches to managing these conditions. Working in partnership with Indigenous health staff and agencies can help ensure that appropriate access to treatment and quality treatment delivery occurs.