OBJECTIVE Oxidative stress may be the unifying mechanism underlying the development of comorbidities in obesity. Evidence suggests that a clustering of sources of oxidative stress exists in obesity: hyperglycemia, hyperleptinemia, increased tissue lipid levels, inadequate antioxidant defenses, increased rates of free radical formation, enzymatic sources within the endothelium, and chronic inflammation. METHODS This review provides a summary of the available evidence on systemic oxidative stress in humans and specific metabolic pathways by which obesity may elevate systemic oxidant stress. The authors suggest possible methods of reducing oxidative stress such as antioxidant supplementation, caloric restriction and/or physical activity and surgical intervention to combat free radicals and reduce adipose tissue. RESULTS Obesity is associated with oxidative stress and can be reduced with weight loss (regardless of exercise or surgery induced weight loss), caloric restriction or antioxidant rich diets. CONCLUSIONS Oxidative stress levels are elevated in human obesity, and these levels are modifiable with various lifestyle modifications and surgical interventions.