Practice guidelines are important tools for improving the delivery of evidence-based practices and reducing inappropriate variation in current treatment approaches. This study examined the degree to which guidelines targeted to the treatment of substance use disorders or serious mental illness address treatment of co-occurring disorders. Guidelines archived by the National Guideline Clearinghouse (NGC) were retrieved in December 2007 and content analyzed. Nineteen pertinent guidelines were identified, and 11 included recommendations regarding the assessment and/or treatment of co-occurring disorders. None of the guidelines making recommendations for treatment of co-occurring disorders included outcomes that clearly targeted both substance use and mental health disorders. Limitations and implications of this study are noted.