Background: Obesity is a major concern among American Indians and Hispanics. The Child Health Initiative for Lifelong Eating and Exercise (CHILE) is an evidence-based intervention to prevent obesity in children enrolled in 16 Head Start (HS) Centers in rural communities. The design and implementation of CHILE are described. Methods: CHILE uses a socioecological approach to improve dietary intake and increase physical activity. The intervention includes: a classroom curriculum; teacher and food service training; family engagement; grocery store participation; and health care provider support. Results: Lessons learned from CHILE include the need to consider availability of recommended foods; the necessity of multiple training sessions for teachers and food service; the need to tailor the family events to local needs; consideration of the pro?t needs of grocery stores; and sensitivity to the time constraints of health care providers. Conclusions: HS can play an important role in preventing obesity in children. CHILE is an example of a feasible intervention that addresses nutrition and physical activity for preschool children that can be incorporated into HS curricula and aligns with HS national performance standards.