Despite the high prevalence of co-occurring mental health and substance-use disorders, there has been a relative lack of treatment research with this population, and the existing research often has limited validity. This article explores some of the barriers to the conduct of research on promising interventions for substance-abuse treatment for people with co-occurring disorders, using the concepts of external and ecological validity to make recommendations for future investigation. The central recommendation is to move rapidly from efficacy studies to more credible and valid effectiveness studies, in order to facilitate the adoption of evidence-based interventions in routine practice settings.