Use this summary report to properly interpret 2021 NSDUH estimates of substance use and mental health issues. The report accompanies theannual detailed tablesand covers overall methodology, key definitions for measures and terms used in 2021 NSDUH reports and tables, and selected analyses of the measures and how they should be interpreted.The report is organized into six chapters:Introduction.Description of the survey, including information about the sample design, data collection procedures, and key aspects of data processing such as development of the analysis weights. The report also includes methodological changes and related issues in the 2021 NSDUH due to COVID-19.Technical details on the statistical methods and measurement, such as suppression criteria for unreliable estimates, statistical testing procedures, issues around selected substance use and mental health measures, and the impact of methodological changes on response rates.Special topics related to prescription psychotherapeutic drugs.A comparison between NSDUH and other sources of data on substance use and mental health issues, including data sources for populations outside the NSDUH target population.A more in-depth view of special methodological issues for the 2021 NSDUH, including the results of special analyses that led SAMHSA to not compare estimates from 2021 to estimates from previous years.An appendix covers key definitions used in NSDUH reports and tables.