There is evidence to support that low fitness and physical activity, excess body weight, and excess abdominal fatness are associated with increased health risk. Moreover, evidence exists to support that sufficient levels of physical activity can significantly improve body weight, fatness, and health risk. Physical activity has been shown to have a modest effect on body weight that is typically <3% of initial body weight, but has an additive effect when combined with dietary restriction. Moreover, physical activity has been shown to be an important behavioral factor for enhancing long-term weight loss and minimizing weight regain; however, this may require relatively high doses of physical activity that approach 300 min/week. Physical activity may concurrently reduce abdominal adiposity, and which may serve as a pathway by which there is also an improvement in health-related risk factors for various chronic diseases. There are important areas of research that require further investigation, with particular need to further examine the dose of physical activity that significantly affects these health outcomes. Moreover, there is a need for improved interventions to promote the adoption and long-term maintenance of physical activity, which can lead to improved weight control, abdominal adiposity, and chronic disease risk factors. Future research is also needed to understand the physiological/metabolic pathways and mechanisms that explain the influence of physical activity on long-term regulation of body weight.