This study recruited 567 African American youth (mean age = 15.27 years; 65.1% girls) to examine the role of parent and peer contexts on drug use among African American adolescents. Data were collected on demographics, drug refusal efficacy, drug use, and various psychosocial factors including family and peer factors. When controlling for age and gender, parental monitoring and peer risky behavior completely mediated the relationship between parental attitudes toward drug use and drug refusal efficacy and partially mediated the relationship between parental attitudes toward drug use and current alcohol use. Only peer risky behavior mediated the relationships between parental attitudes toward drug use and current tobacco and marijuana use. Results also revealed several salient moderating relationships. Implications for prevention programs are provided and include strengthening current parenting skills and focusing efforts on fostering the mother-adolescent relationship.