The purpose of this review was to determine the effectiveness of physical activity in improving chronic disease risk factors in obese individuals. A systematic review was conducted to identify randomized physical activity intervention studies reporting changes in risk factors among obese individuals published prior to March 2010. Studies included in the review were randomized trials of at least 10 weeks in duration, with a sample mean body mass index ≥30 kg/m2 at baseline, and reporting a relevant risk factor (blood pressure, blood lipids, glucose/insulin or C-reactive protein). Forty-four studies met the inclusion criteria for this review. Overall, physical activity had no more than a modest effect on chronic disease risk factors in obese individuals. There was great heterogeneity in responses of risk factors across studies. In many studies it was difficult to determine the effect of physical activity, independent of changes in body mass consequent to the intervention. Obese individuals should be encouraged to undertake physical activity following general recommendations for weight loss and health. The degree to which physical activity is effective at lowering risk factor levels among high-risk obese individuals is not known.