Monitoring the Future (MTF) is a long term study of substance use and related factors among U.S. adolescents, college students, and adult high school graduates through age 60. It is conducted annually and supported by the National Institute on Drug Abuse. MTF findings identify emerging substance use problems, track substance use trends, are published with many scientific results, and help to inform policy and intervention strategies. The key findings regarding use of various substances by 8th, 10th, and 12th graders surveyed across the U.S. in 2021 are summarized below. But first a few words about the context. The preceding year, 2020, was an unusual year for the study in that data collection was halted earlier than usual, in March of that year, due to the emerging COVID-19 epidemic and the University of Michigan halting in-person research. This resulted in smaller samples being obtained that year, but based on careful analyses we believe that the smaller samples reflect drug use for all students that year with reasonable accuracy. The previous year, 2019, was unusual in a different way--it was the year that the study was transitioning from using paper and pencil questionnaires in schools to having students use electronic tablets. A random half of all respondents in 2019 used the older mode of administration, while the other half used tablets. How the authors e dealt with these two disruptions to the ongoing series is described in the section on Study Design and Methods. It should be noted that the 2020 data collection occurred early in 2020, covering the early months of the epidemic, but it did not cover most of the period of the epidemic that year, nor of its effects. However, the 2021 data collection occurred more than a year into the COVID epidemic and brought quite dramatic changes in adolescent drug use in the United States. A synopsis of the design and methods used in the study follows the introductory section. A separate section is then provided for each individual drug class, including figures that show trends in the overall proportions of students at each grade level (1) using the drug; (2) seeing a "great risk" associated with its use (perceived risk); (3) disapproving of its use (disapproval); and (4) saying that it would be "fairly easy" or "very easy" to get if they wanted to (perceived availability). For 12th graders, annual data are available since 1975--and for 8th and 10th graders since 1991, the first year they were included in the study. The tables at the end of this report provide the statistics underlying the figures; in addition, they present trend data on lifetime, annual, 30 day, and (for selected drugs) daily prevalence. [For "Monitoring the Future National Survey Results on Drug Use, 1975-2020: Overview, Key Findings on Adolescent Drug Use," see ED611736.]