With the increasing prevalence of obesity and type 2 diabetes mellitus in the general population, nonalcoholic fatty liver disease (NAFLD) has become a common diagnosis in clinical practice. Insulin resistance and oxidative stress play an important role in NAFLD development and progression. NAFLD affects one in three adults and one in 10 children/adolescents in the United States. Mortality in patients with NAFLD is significantly higher than in the general population of same age and gender with liver-related complications. Lifestyle intervention may improve NAFLD, but medications that increase insulin sensitivity and the anti-oxidant defenses in the liver deserve evaluation in carefully controlled trials.