The prevalence of obesity is high and continues to increase. Obesity is a leading risk factor for premature mortality and numerous chronic health conditions. The role of physical activity as a treatment and (or) preventive strategy for combating obesity has been the subject of substantial research. Most of this research has focused solely on reductions in total body weight and (or) fat mass as the indicator of treatment success. Because the deposition of fat in the abdomen and nonadipose tissues of the liver and muscle plays a major role in the development of obesity-related health risk, these depots have emerged as alternative targets for obesity treatment. Absent from previous reviews is a detailed consideration of the influence of physical activity on these treatment outcomes. The purpose of this review is to evaluate the independent role of physical activity in the treatment of obesity in a broader context; that is, through its effects on abdominal obesity and liver and muscle fat, in addition to its established effects on body weight and (or) total fat mass. Consideration is also given to the utility of physical activity with minimal or no weight loss in the treatment of obesity.