National efforts are underway to integrate medical care and behavioral health treatment. This special issue of the Journal of Substance Abuse Treatment presents 13 papers that examine the integration of substance use interventions and medical care. In this introduction, the guest editors first describe the need to examine the integration of substance use treatment into medical care settings. Next, an overview of the emerging field of implementation science and its applicability to substance use intervention integration is presented. Preview summaries of each of the articles included in this special issue are given. Articles include empirical studies of various integration models, study protocol papers that describe currently funded implementation research, and one review/commentary piece that discusses federal research priorities, integration support activities and remaining research gaps. These articles provide important information about how to guide future health system integration efforts to treat the millions of medical patients with substance use problems.