The ultimate success of preventive interventions relies on their ability to engage and influence the growing presence of subcultural groups. To encourage and guide the development of effective preventive intervention for subcultural groups, four approaches are described, illustrated, and critiqued with respect to their considerations of cultural fit, reach, efficacy and adoption. Those approaches are (a) the prevention research cycle, (b) cultural adaptations of evidence-based interventions, (c) investigator-initiated culturally-grounded approaches, and (d) community-initiated indigenous approaches. Special attention is given to recent advances in the specification of stages in the cultural adaptation of interventions. The paper closes with some conclusions and topics in need of greater attention.