The current review conducted a systematic assessment of culturally sensitive risk prevention programs for African American adolescents. Prevention programs meeting the inclusion and exclusion criteria were evaluated across several domains: (1) theoretical orientation and foundation; (2) methodological rigor; (3) level of cultural integration; (4) program target or domain (e.g., schools, communities, families); (5) outcome change level assessed (e.g., addressing change in beliefs/values or behaviors); and (6) program effects on risk behaviors. Thirteen studies (N = 13) with adolescent participants ranging from 10 to 18 years were identified and evaluated. Analyses suggested that more effective culturally sensitive risk prevention programs included the following: (1) a clearly articulated theoretical orientation, which utilized both universal (e.g., behavioral theories) and culturally specific (e.g., Africultural theories) frameworks; (2) a rigorous methodological design (e.g., inclusion of control group, utilization of program manuals, valid and reliable study measures); (3) an integration of culture at multiple levels (e.g., accessibility, delivery, and content) of programming; (4) consideration of the influence of multiple contexts and domains (e.g., family, community, school); (5) multiple behavior change outcomes (e.g., behaviors, relationships, values); and (6) sustained program effects over time. Recommendations for increasing the effectiveness and efficacy of culturally sensitive prevention programs are discussed.