The frequency of overweight and obesity among North American Indian children and youth exceeds that of other ethnic groups in the United States. This observation is based on studies using body mass index as the primary measure of overweight and obesity. In the mid-20th century, there were regional differences among North American Indian groups in sub-adults’ size and shape and only a few Southwestern groups were characterized by high rates of overweight and obesity. In most populations, the high prevalence of overweight and obesity developed in the last decades of the 20th century. Childhood obesity may begin early in life as many studies report higher birth weights and greater weight-for-height in the preschool years. Contributing factors include higher maternal weights, a nutritional transition from locally caught or raised foods to store bought items, psychosocial stress associated with threats to cultural identity and national sovereignty, and exposure to obesogenic pollutants, all associated to some degree with poverty. Obesity is part of the profile of poor health among Native Americans in the US and Canada, and contributes to woefully high rates of diabetes, cardiovascular disease, and early mortality. Interventions that are culturally appropriate are needed to reduce weights at all points in the lifespan.