The Zuni Life Skills Development Program, an effective community-initiated and high-school-based suicide prevention intervention, is featured. Development and evaluation of this intervention are followed by note of the specific challenges associated with stabilizing the program. A more tribally diverse, culturally-informed model entitled the American Indian Life Skills Development Curriculum is then presented to illustrate a hybrid approach to the cultural tailoring of interventions. This curriculum is broad enough to address concerns across diverse American Indian tribal groups yet respectful of distinctive and heterogeneous cultural beliefs and practices. Finally, we reflect upon issues in community-based research that emerged during this collaboration.