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The authors review and evaluate the literature and guidelines on care for individuals with a co-occurring affective or anxiety disorder and substance use disorder.MEDLINE and PsycINFO computerized searches of the English language literature were conducted for the period 1990–2002. These articles were supplemented with searches of the Cochrane Database of Systematic Reviews (1990 to 2002) and with articles that were sent to the authors by experts in the field to review. Bibliographies of selected papers were hand searched for additional articles. From these searches a total of 219 articles were found, of which 127 were selected for review.The literature shows that, over the past several decades, treatment for co-occurring disorders has undergone a broad shift in approach, from treating substance abuse before providing mental health care to providing simultaneous treatment for each disorder, regardless of the status of the comorbid condition. Many treatment recommendations are supported by a broad consensus. However, despite this broad agreement, recommendations are often not specific enough to guide clinical care. Most recommendations with specificity are for acute pharmacotherapy, but even specific recommendations lag behind current clinical practice. Although the use of psychotropic medication for mental illness is encouraged, experts disagree as to whether it is necessary to wait for abstinence before beginning pharmacotherapy. In addition, most diagnosis-specific guidelines are silent as to whether the specific treatment recommendation applies to co-occurring disorders. Finally, empirical evidence is lacking for most recommendations. The authors conclude that the mental health and substance abuse treatment fields need to consider its research priorities and how to address the multitude of potential combinations of disorders.