This article examines issues and challenges in the design of cultural adaptations that are developed from an original evidence-based intervention (EBI). Recently emerging multistep frameworks or stage models are examined, as these can systematically guide the development of culturally adapted EBIs. Critical issues are also presented regarding whether and how such adaptations may be conducted, and empirical evidence is presented regarding the effectiveness of such cultural adaptations. Recent evidence suggests that these cultural adaptations are effective when applied with certain subcultural groups, although they are less effective when applied with other subcultural groups. Generally, current evidence regarding the effectiveness of cultural adaptations is promising but mixed. Further research is needed to obtain more definitive conclusions regarding the efficacy and effectiveness of culturally adapted EBIs. Directions for future research and recommendations are presented to guide the development of a new generation of culturally adapted EBIs.