Developed by the Center for Substance Abuse Treatment (CSAT), part of the Substance Abuse and Mental Health Services Administration (SAMHSA), the best-practice guidelines presented here are the result of clinical, research, and administrative experience and knowledge. The approach adopted in this opioid treatment protocol is that opioid addiction is a medical disorder than can be effectively treated with medications administered within a treatment model that incorporates supportive services including psychosocial counseling, treatment for co-occurring disorders, medical services, and vocational rehabilitation. The handbook provides a detailed description of medication-assisted treatment for opioid addiction (MAT), particularly for use in opioid treatment programs (OTPs). Optional approaches are built into the MAT protocol, such as comprehensive maintenance treatment, medical maintenance treatment, detoxification, and medically supervised withdrawal. The treatment protocol also addresses a variety of issues and challenges that may arise during MAT, such as how and when to conduct drug testing for screening and assessment purposes; issues of safety and noncompliance among clients; complications arising from co-occurring substance use disorders and co-occurring mental health disorders; and administrative issues concerning procedures and staffing. The history of medication-assisted treatment for opioid addiction is reviewed, as is the pharmacology of medications used to treat opioid addiction. Medical problems associated with opioid addiction are reviewed and a protocol is set forth for providing medication-assisted treatment during pregnancy. Appendixes address ethical considerations regarding the administration of MAT. Exhibits, appendixes, bibliography