Obesity touches the lives of most Americans regardless of age. In adults, accrual of co-morbidities, including frank disability, impacts health in ways that mandate aggressive public health action. In children, the rising prevalence of overweight and obesity raises serious prospective concerns for life as these children enter adulthood. Action is imperative to provide medical interventions and preventive strategies to reduce the threat this condition poses to future generations. Obesity primarily results from an energy regulation imbalance within the body; understanding its origin and effects requires considering both the intake (via eating) and output (via moving) of energy. This article focuses on how exercise and physical activity (i.e., energy output) can influence the primary condition of obesity and its health sequelae. Components, strategies, and expected outcomes of exercise and lifestyle activity are addressed. Successful long-term participation in daily movement requires matching exercise regimens and physical activity outlets to individual preferences and environmental conditions. Activity habits of Americans must change at home and in the workplace, schools and the community to positively influence health. Although the goals of Healthy People 2010 to reduce sedentary behavior have not been met, success of other public health interventions (e.g., immunizations, use of bicycle helmets) suggests that social change to alter activity habits can be achieved. Failure to reach our public health goals should serve as a catalyst for broad-based action to help children, adolescents, and adults attain and maintain behaviors that reduce the risk of obesity and its health insults. Pediatr Blood Cancer 2012; 58: 135–139. © 2011 Wiley Periodicals, Inc.