Hypertension has been associated with several modifications in the function and regulation of the sympathetic nervous system (SNS). Although it is unclear whether this dysfunction is primary or secondary to the development of hypertension, these alterations are considered to play an important role in the evolution, maintenance, and development of hypertension and its target organ damage. Several pharmacological antihypertensive classes are currently available. The main drugs that have been clearly shown to affect SNS function are beta-blockers, alpha-blockers, and centrally acting drugs. On the contrary, the effects of ACE inhibitors (ACE-Is), AT1 receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics on SNS function remain controversial. These properties are pharmacologically and pathophysiologically relevant and should be considered in the choice of antihypertensive treatments and combination therapies in order to achieve, beyond optimal blood pressure control, a normalization of SNS physiology and the most effective prevention of target organ damage.