The high prevalence of obesity among American Indian children and the associated health and financial burdens warrant strong and effective prevention efforts. While the prevention of childhood obesity has risen to the top of the list of public health priorities, relatively little research has focused on childhood obesity prevention, especially for high-risk populations. The development and evaluation of innovative, culturally appropriate, and effective strategies to prevent excessive weight gain is critical, particularly for American Indian youth. Early prevention efforts are especially important given the substantial evidence that eating and physical activity habits are established in early childhood and continue into adulthood. Adopting healthy eating and physical activity habits early in life is an effective way of preventing obesity and related diseases. The best intervention to prevent obesity in children should target the two most prominent influences on the young child's eating and physical activity behaviors: the school and the family. Obesity in American Indian children begins very early in life, which suggests that interventions need to begin early. Research has shown that 43% of American Indian 5-6 year olds in South Dakota are already overweight. Thus, targeting children in this young age group may be advantageous.