Non-alcoholic fatty liver disease (NAFLD) is the most common cause of pediatric liver disease. Similar to NAFLD in adults, NAFLD in children is associated with obesity and insulin resistance and requires liver histology for diagnosis and staging. However, significant histological differences exist between adult and pediatric NAFLD. The rise in childhood obesity has been accompanied by an increase in pediatric NAFLD. Age, gender and race/ethnicity are significant determinants of risk, and sex hormones, insulin sensitivity and adipocytokines are implicated in the pathogenesis of pediatric NAFLD. There is no consensus for treatment of NAFLD, however, data suggest that diet, exercise and some pharmacological therapies may be of benefit. To evaluate and effectively treat pediatric NAFLD, the pathophysiology and natural history of the disease should be clarified and non-invasive methods for screening, diagnosis, and longitudinal assessment developed.