This study examined illicit substance use among 1,004 adolescents, ages 11-21, involved with the Child Welfare System (CWS) and followed from 1999 to 2007. By the time they reached transition age, more than 60% of the sample had used an illicit substance in their lifetime. Predictors of regular use during adolescence were having a prior CWS report, externalizing behavior problems, delinquency, and any sexual experience. Exposure to physical abuse was predictive of escalating substance use trajectories. Protective factors included having a child at any point during the study, parental monitoring, and being placed in kinship care.