Central neural mechanisms play a key role in the maintenance of cardiovascular homeostasis. Alterations in neuro-cardiovascular regulation are implicated in pathological states such as hypertension and heart failure, and angiotensin II (Ang-II) figures prominently in the underlying mechanisms of these disesases. Abundant evidence now suggests that a key mechanism by which Ang-II influences the cardiovascular system is via its ability to produce reactive oxygen species (ROS). However, most research to date in this area has focused on peripheral tissues such as the vasculature and kidney. Accumulating evidence suggests that ROS have important effects on central neural mechanisms involved in blood pressure regulation, volume homeostasis, and autonomic function, particularly those that involve Ang-II signaling. Ang-II stimulates ROS production and redox-regulated molecules in cultured neurons isolated from cardiovascular regulatory nuclei of the central nervous system. Furthermore, genetic overexpression of ROS scavenging enzymes selectively in these brain regions prevents the pathological effects of Ang-II on blood pressure, heart rate and sympathetic nerve activity in experimental models of hypertension and heart failure. Studies suggest that specific members of the NADPH oxidase (Nox) enzyme family play a key role in Ang-II-mediated generation of ROS in central cardiovascular neurons, and that brain site-selective silencing of certain Nox homologues by viral delivery of RNAi blunts the physiological actions of Ang-II in the brain. Studies are ongoing to define the downstream molecules activated