This thesis aimed at understanding initiation and escalation of substance use among young people. We first identified prototypical patterns and trajectories of substance use, providing valuable information on how progression and intensification occur. We then discuss the early-onset problem, showing the stability of substance use over time among young adults and how early initiation was associated with substance use escalation. We recommend that future empirical studies and prevention programs: 1) target early adolescence to delay substance use initiation, 2) use harm reduction measures to reduce detrimental outcomes associated with substance use, 3) consider polysubstance use as the major substance use pattern, 4) focus on substance use among people with psychiatric disorders, and 5) target critical life outcomes, such as disengagement and forgone care. Targeting these important issues would improve young people's health and reduce health inequalities.