This dissertation focuses on key conceptualizations of adolescent substance use that are used in science, policy, and prevention to calibrate societal responses to related problems. It examines how such conceptualizations and other ways of providing meaning to both legal and illegal substance use function in explaining who these users are and how their use develops over time. The ambition is also to study how adolescents, upon reaching young adulthood, provide meaning to substance use and to what extent dominant conceptualizations are reflected in their lay discourse. The conceptualizations addressed include the Risk Factor Model, the Normalization Thesis, the Gateway Theory, and the discourse of neoliberalism. The dissertation consists of four studies that are based on quantitative survey data and qualitative interview data from the Futura01 cohort; a representative sample from the normal population of adolescents. The data cover three time points: survey data from 2017 (participants’ age: 15/16) and 2019 (age: 17/18), and interview data from 2022-23 (age: 21/22). Study I use regression analysis to explore the association between risk factors and substance use at two time points. Study II employs latent transition analysis to identify clusters of adolescent substance users and how adolescents transition between these clusters over time. Study III uses the Logics of Critical Explanation framework to examine how substance use, risk factors, and future prospects are understood by young adults in qualitative interviews. Finally, Study IV uses a narrative approach to explore how young adults understand their own transition out of adolescent substance use and into responsible adulthood. The studies jointly found support in the Swedish normal population for some of the above-mentioned conceptualizations, while others fell short. The Risk Factor Model and the Normalization Thesis could partially explain adolescent substance use. For instance, some micro-level risk factors were stable predictors of substance use as they could predict use of both legal and illegal substances, both in 9th and 11th grade. Others could predict use of certain substances or use at specific time points, or fail to predict at all. However, this dissertation found little support for the Gateway Theory. Although these conceptualizations are primarily utilized in quantitative research, they were prominently reflected in the participants’ lay discourse, as expressed during the research interviews. Furthermore, the participants primarily conceptualized substance use through neoliberal ideals such as individualism, moderation, and health. The use of both legal and illegal substances was understood as something enjoyable and, in part, as a practice associated with adolescence. However, participants believed that substances should not be used to the extent that they would jeopardize a successful transition into adulthood. For them, this stance was associated with a process of maturing out of substance use during their early 20s, as well as maintaining a permanent state of vigilance if they choose to try or use legal or illegal substances after this period in life. In correspondence with the setup of substance use prevention and policy in Sweden, the participants seemed to favor conceptualizations whose point of departure was individualism. The dissertation closes with a discussion about whether this far-reaching focus on substance use as individual choice risks obscuring alternative conceptualizations and societal responses that highlight the influence of structural factors on deviant behavior such as adolescent substance use.