Six models were tested examining the risk and protective factors of substance use during the transition from middle to high school. The study sample included 321 families (an adult and an 8th grader) in order to assess the concurrent and prospective relationships between parenting (effective and ineffective), peer association (prosocial and deviant), and adolescent drug use and attitudes about drug use. Non-mediated as well as peer mediated non-gender specific and gender-specific structural equation models were tested for both risk and protective models. The risk models indicated consistent and developmentally persistent concurrent, prospective, and reciprocal associations among ineffective parenting, deviant peer associations, and adolescent drug use and attitudes. Specifically, ineffective parenting has direct and mediated effects on adolescent drug use during that transition from middle to high school in the non-gender specific models. Deviant peer association had a prospective relationship with ineffective parenting during this developmental transition. The mediated gender-specific risk model showed relatively minor gender differences. In the non-gender specific protective models, effective parenting had largely concurrent relationships between prosocial peer association and adolescent drug use and attitudes. There are more prominent gender differences in the protective model, as for females there are consistent and resilient concurrent and reciprocal prospective relationships between effective parenting, prosocial peer association, and adolescent drug use and attitudes. Overall, the results suggest that the transition from middle school to high school is a critical juncture for risk factors for adolescent drug use and attitudes. Additionally, the protective models suggested that effective parenting strategies may have more effects earlier in development