Sympathetic activation characterizes essential hypertension, contributing to the development and progression of the high blood pressure state. Throughout the years, evidence has been accumulated to show that adrenergic overdrive also participates in the pathogenesis of the end-organ damage associated with hypertension, including cardiac hypertrophy, left ventricular diastolic dysfunction, and heart failure, as well as the vascular structural and functional alterations that frequently can be detected in large, medium-size, and small arteries. Adrenergic overdrive also participates in the renal insufficiency and failure that may accompany the clinical course of the hypertensive state. This paper reviews evidence collected over the past few years documenting the importance of neurogenic factors in the development and progression of end-organ damage. The therapeutic implications of this evidence are also highlighted.