Normally, the kidney plays the dominant role in setting long-term arterial pressure, and the nervous system acts primarily as a short-term regulator, adjusting arterial pressure to acute challenges (eg, standing, running, and stress). However, in several animal models and in subsets of hypertensive human patients, the nervous system seems to play a more significant role in the chronic elevation of arterial pressure. Many clinical studies suggest that the peripheral sympathetic nerves are intimately involved in hypertension, and researchers recently characterized abnormalities in the brain that seem to predispose animal models to sympathetic nervous system overactivity and hypertension. Together, the current data strongly suggest that the brain, via the sympathetic nervous system, directly contributes to some forms of hypertension and indirectly contributes to all of them. This review is not intended as an exhaustive examination of all studies on the role of the nervous system in hypertension but rather focuses on several intriguing experiments that provide provocative new insights on this topic.