Self-report data regarding alcohol, cigarette, and marijuana use were collected biennially from ages 14 to 20 in a nationally representative panel sample of adolescents (N=1,897) from the Monitoring the Future study. Growth curve analyses were performed using hierarchical linear modeling to consider psychosocial background, motivation and school attitudes, and parental and peer influences at age 14 as predictors of concurrent substance use and change in substance use. Results indicated that school misbehavior and peer encouragement of misbehavior were positively associated with substance use at age 14 and with increased use over time; school bonding, school interest, school effort, academic achievement, and parental help with school were negatively associated. The protective effects of positive school attitudes and perceptions of high status connected to academics were stronger for low-achieving compared with high-achieving youth. Implications for a developmental perspective on substance use etiology and prevention are discussed.