Adolescence is a developmental period during which many youth experiment with risk practices. This paper examined the association of parental monitoring with a range of alcohol and other drug (AOD) use behaviors among high-risk youth, while controlling for other demographic and environmental variables previously found to be associated with AOD use. Participants were recruited as part of a longitudinal evaluation study of four youth drop-in centers located in Southern California. These centers served at-risk youth, including Hispanic, Lesbian/Gay/Bisexual/Questioning (LGBQ), and homeless and runaway youth. Participants were aged 14 to 24 and were new attendees at the drop-in centers. Results from logistic regression analyses revealed that while controlling for demographic and environmental variables, adolescents who reported less parental monitoring were more likely to report lifetime use of cigarettes, marijuana, and methamphetamine, and in the past three months, use of alcohol and binge drinking. The findings thus indicate that, even among high-risk youth, those who reported low parental monitoring were significantly more likely to use a variety of substances. Implications of these findings are discussed as they pertain to AOD prevention and interventions for children and their families.