What is already known about this topic? Use of the prescription opioid methadone for treatment of pain, rather than for treatment of opioid use disorder, has been identified as an important contributor to the rise in opioid-related overdose deaths. In recent years, a number of actions to reduce the use of methadone for pain treatment have been taken. What is added by this report? During 2002-2006, the national distribution rate of methadone increased, on average, 25.1% per year, methadone-involved drug overdose deaths increased 22.1% per year, and methadone diversion increased 24.3% per year. After 2006, methadone distribution declined 3.2% per year, and methadone-involved overdose deaths declined 6.5% per year. Rates of methadone diversion continued to increase during 2006-2009, but substantially more slowly, and then declined an average of 12.8% per year beginning in 2010. By sex, most age groups, race/ethnicity, and U.S. Census region, the methadone overdose death rate peaked during 2005-2007 and declined in subsequent years. Persons aged 25-54 years had the highest overdose death rates during the study period. There was no significant change in the overdose death rate trend among persons aged ≥65 years, who also had the lowest overdose death rate. Among persons aged 55-64 years, the rate of methadone overdose deaths continued to increase through 2014. What are the implications for public health practice? Additional clinical and public health policy changes are needed to further reduce methadone-related harm, especially among persons aged ≥55 years. © 2016, Department of Health and Human Services. All rights reserved.