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Methadone is familiar to most laypersons as a treatment for heroin addiction, dispensed at special clinics. Methadone is also a powerful, inexpensive, and effective analgesic, but it has many unique and potentially lethal aspects that have to be well understood before using it for pain relief. Addiction treatment with methadone requires a special license, but any provider who can prescribe Schedule II medications can write for methadone for pain. Unfortunately, because no special training is required to prescribe methadone and because poor insurance coverage is leading to the increased use of inexpensive methadone, there has been a tragic dramatic increase in opioid deaths attributed to methadone. This chapter reviews the indications, contraindications, drug interactions, metabolism, genetic issues, ethics, and initial evaluation and treatment for methadone.