Methadone is a long-acting synthetic opioid with high affinity for various opioid receptors, especially for m-opioid receptors. Methadone has been used as a successful pharmacologic intervention for the treatment of heroin dependence and acute and chronic pain. This treatment is effective for opiate addiction, reducing morbidity and mortality associated with heroin use. However, overdosing with methadone has become a growing phenomenon because of the increased availability of this drug. Patients enrolled in a methadone maintenance treatment program may become physically dependent and may experience methadone withdrawal symptoms. In this review article, there are discussed about pharmacokinetic and pharmacodynamic properties of methadone, clinical symptoms of its overdose, dosage problems, detection of methadone in biological samples, treatment, and causes of methadone overdose-related deaths.