Technical Abstract: Childhood obesity is a complex disease influenced by genetic and environmental factors and their interactions. The current surge in childhood obesity in the United States is attributable to an interaction between a genetic predisposition toward obesity and a permissive environment. Several recent systematic reviews and meta-analyses have been published on the association between breast-feeding and childhood obesity. In these analyses, adjustment for confounding factors attenuated or nullified the protective effect of breast-feeding on later obesity. The Viva La Familia Study was designed to identify genetic and environmental factors affecting obesity and its comorbidities in 1030 Hispanic children from 319 families. Odds ratios for potential risk factors associated with childhood overweight were computed using binary logistic regression for panel data. Early infant-feeding practices were not significant. Salient independent risk factors for childhood obesity in this cohort of Hispanic children were age, birth weight, maternal obesity, paternal obesity, number of children in the family, and the percentage of awake time spent in sedentary activity. Breastfeeding may have a small protective effect against childhood obesity, although residual confounding may exist. Human milk is exquisitely fitted for optimal infant growth and development and may uniquely modulate neuroendocrine and immunologic pathways involved in the regulation of body weight. Nevertheless, other genetic and environmental determinants such as socioeconomic status, parental obesity, smoking, birth weight, and rapid infancy weight gain far supersede infant-feeding practices as risk factors for childhood obesity.