ABSTRACT This application seeks a five-year continuation of the Monitoring the Future (MTF) study, an ongoing epidemiological and etiological research and reporting project begun in 1975. In addition to being a basic research study, MTF has become one of the nation's most relied upon sources of information on emerging trends in illicit drug, alcohol, and tobacco use among American adolescents, college students, and adults. Nationally representative samples of 8th, 10th, and 12th grade students (about 42,000 students per year) will be surveyed annually from 2022/23 to 2026/27. A companion panel application seeks continuation of follow-up surveys of both past and future high school graduates at modal ages 19–30, 35, 40, 45, 50, 55, 60, and, new to this cycle, age 65. The study's cohort-sequential longitudinal design permits the measurement and differentiation of three types of change—age (developmental), period (historical), and cohort. Each has different determinants, and MTF finds all three types of change occur for most drugs. Factors that may explain historical trends and cohort differences also are monitored. MTF is designed to document the developmental history and consequences of drug use and related attitudes from adolescence through the retirement years, and to determine the individual and contextual characteristics and social role transitions that contribute to change and stability in both use and related attitudes. This work will be extended to new years, cohorts, and ages under this main application and the companion follow-up application. The study will examine the importance of many other hypothesized psychological, behavioral, and social determinants of drug use (including attitudes and beliefs, counter- advertising, role-modeling, and access), as well as a range of potential consequences (including physical and psychological health, status attainment, role performance, and symptoms of substance use disorders). Impacts of policy changes will be examined, including new FDA policies aimed at the reduction of teen vaping. The study's very broad measurement covers (a) initiation, use, and cessation for over 50 categories and subcategories of licit and illicit drugs, including alcohol and tobacco; (b) attitudes and beliefs about many of them, including perceived risk of harm, disapproval, and perceived availability; (c) other behaviors and individual characteristics (health difficulties, delinquency, school performance, plans, aspirations, etc.); and (d) aspects of key social environments (home, work, school) and social role statuses, experiences, and transitions. Results will continue to elucidate drug use from adolescence through adulthood—including the introduction of new drugs—with major implications for policy, research, treatment, and prevention agendas.