Sympathetic hyper-activity and diminished parasympathetic activity are a consequence of many primary cardiovascular disease states and can trigger arrhythmias. Emerging evidence suggests that reactive oxygen species (ROS) including nitric oxide, superoxide, and peroxynitrite may contribute to cardiac sympathovagal imbalance in the brainstem, peripheral neurons, and in cardiomyocytes since all experience increased oxidative stress as a result of cardiac disease processes and aging. This article reviews the roles of ROS in autonomic dysfunction and arrhythmia. In addition, novel research directed toward finding targets for modulating sympathovagal balance in cardiac disease is discussed.