Contrary to expectations, we found that, for the entire sample, mean parental knowledge was not associated with decreases in adolescent substance use rates over the one-year period (i.e., the slope), but increased parental knowledge was a significant concurrent predictor of decreases in substance use. Considered in combination, these findings suggest that changes in parental knowledge as a likely response to adolescents’ changing developmental needs or behaviors may be especially critical to influencing rates of adolescent substance use.