Latino children experience higher rates of obesity than do non-Latino white children. Family-centered nutrition interventions can slow the rate of weight gain in this population. Niños Sanos, Familia Sana (Healthy Children, Healthy Family) is a 5-year, community-based, participatory research study that targets rural Mexican-origin farmworker families with children aged 2 to 8 years in California's Central Valley. Adaptation of a culturally relevant obesity prevention program involved qualitative research to tailor key obesity prevention messages, pilot testing and implementation of key messages and activities at family nights, and continual modification to incorporate culturally innovative elements. Of the 238 families enrolled, 53% (125) attended the recommended minimum of 5 (of 10 possible) classes during the first year. A university and community partnership can guide development of a culturally tailored obesity prevention program that is suitable for reaching a high-risk Mexican-origin audience through cooperative extension and other public health programs.