Although studies have explored the predictors of changes in rank ordering of adolescent substance use over time, little research has specifically examined the predictors of substance use escalation and de-escalation. The present study tested whether social influences, individual differences, and symptomatology predicted substance use escalation and de-escalation over a 9-month period in a community sample of adolescents (N = 390). Peer substance use, negative affectivity, externalizing symptoms, and internalizing symptoms prospectively predicted substance use escalation. Only peer substance use and parental control predicted de-escalation. Results provide support for the assertion that social influences, individual differences, and symptomatology predict substance use escalation and de-escalation but suggest that the relations differ for alcohol use versus illicit substance use and for the prediction of escalation versus de-escalation.