Both Reactive Oxygen Species (ROS) and hyperactivation of the nutrient-sensing mTOR/S6 kinase cascade have been linked to aging and age-related diseases as well as to the anti-aging effect of calorie restriction. Recent findings that the pro-aging and pro-oxidant molecule p66shc contributes to S6K activation by nutrients and promotes insulin resistance and diabetes in mice may provide an answer to the "ROS or TOR?" dilemma.