This paper draws from a literature review commissioned as part of a larger project evaluating comorbidity treatment service models, which was funded by the Australian Government Department of Health and Ageing as part of the National Comorbidity Initiative. The co-occurrence of mental health and substance use disorders (comorbidity) is a common and complex problem. This paper outlines conceptual and practical complexities and barriers associated with comorbidity treatment service delivery, particularly around the variable nature of comorbidity, and the impacts of the separation of the mental health (MH) and alcohol and other drug (AOD) sectors with their differing institutional cultures, aetiological concepts, philosophical underpinnings, educational requirements, administrative arrangements, and screening and treatment approaches. Issues pertaining to the lack of consistent definitions and conceptual frameworks for comorbidity are discussed, particularly in relation to the reported lack of communication, collaboration, and linkages between the sectors. It is suggested that the adoption of consistent terminology and conceptual frameworks may provide a valuable step towards consistency in service provision and research and could lead to improved capacity to address the many issues relating to comorbidity service provision and treatment efficacy.