Substance use is a developmental disorder, with clear age-graded trends reflecting initiation in adolescence, increased use through emerging adulthood, and a decline thereafter. A developmental framework places substance use behavior both within the context of normal development and in relation to the interplay between environmental and person-specific characteristics, where underlying risk may manifest as a substance use problem in the face of an enabling environment. Individuals have changing vulnerabilities to substance use and related problems that are due to chronological aging as well as attributable to the normative developmental tasks and role transitions that may serve as a turning point directing an individual toward or away from substance use. Against the backdrop of normative patterns are distinct developmental trajectories that are likely linked to different etiological pathways and that, through valid testing of developmental theory, can inform the content and timing of prevention programs targeted to reach high-risk subgroups.