This article attempts to conceptualize the issues, problems, research, and policy solutions that have arisen in Scotland as a result of co-morbid substance misuse and mental health problems in treatment- and non-treatment-seeking populations. This approach also acknowledges the differences and similarities present when comparing the Scottish and national UK responses to co-morbidity. Finally, information and recommendations from a Scotland-wide qualitative research program on co-morbidity will help relate the Scottish picture with the international scene in trying to identify the best ways of tackling this complex situation. (Am J Addict 2007;16:147-159)