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This paper examines prevention programming for African American girls by placing the prevention process within the larger African and African American cultural context. We provide an overview of the theories and issues we consider most relevant to African American culture, including Africentric theory, ethnic identity, gender identity and relational theory, developmental issues, the community context, and historical considerations. Drawing from our own drug prevention work, we provide examples of how to incorporate culture into prevention programs to make them most relevant for the target population. We also summarize our own efforts to create culturally appropriate prevention interventions and their impact on the girls in our programs. We conclude with suggested directions for future research into culture-specific prevention programs.