This research tested for moderation in the relation of family risk factors (parent-child conflict, family life events, and parental substance use) to adolescent substance use (tobacco, alcohol, and marijuana). A sample of 1,810 participants was surveyed at the mean age of 11.5 years and followed with 2 yearly assessments. Temperament dimensions were assessed with the Revised Dimensions of Temperament Survey and the Emotionality, Activity, and Sociability Inventory. Multiple-group latent growth analyses indicated moderation occurred through (a) alteration of effects of parental variables on the adolescent substance use intercept and on the peer substance use intercept and slope and (b) alteration of the effect of the peer substance use intercept on the adolescent substance use slope. The impact of parental risk factors was decreased among participants with higher task attentional orientation and positive emotionality (resilience effect) and was increased among participants with higher activity level and negative emotionality (vulnerability effect). Results from self-report data were corroborated by independent teacher reports.