Comorbidity of substance use disorders and mental disorders is very common, and there is substantial heterogeneity within subgroups in terms of both their characteristics and the nature of causal relationships between the disorders. Assessment and management strategies need to deal with both the size of the problem across the community and its severe impact in some subgroups, including those with psychosis. At this stage, the research base from which we can derive recommendations is very narrow, but it does offer a foundation for preliminary conclusions. This chapter reviews the current evidence and makes some suggestions for assessment and for both psychological and pharmacological management.