Muscle sympathetic nerve activity (MSNA) has shown that sympathetic activation may occur in essential hypertension (EHT). However, the small sample size of the studies, the heterogeneity of the patients examined, and the presence of confounders represented major weaknesses not allowing to draw definite conclusions. Among the 432 studies identified providing information in EHT on MSNA, 63 were eligible (1216 patients) and meta-analyzed grouping them on the basis of clinically relevant questions: (1) Is MSNA increased in hypertension of mild/moderate-to-severe degree? (2) Does sympathetic activation occur in borderline, white-coat, and masked EHT? (3) Is MSNA related to clinic and ambulatory blood pressure and target organ damage? (4) Are heart rate and venous plasma norepinephrine valuable surrogate markers of MSNA in clinical practice? The results show that MSNA was significantly greater (1.5×; P<0.001) in mild-to-moderate and severe EHT as compared with normotensive controls and that this was the case also in borderline, white-coat, and masked hypertension as well. Interestingly, MSNA was significantly greater in both untreated and treated hypertension (P<0.001 for both), related to clinic and ambulatory blood pressure (r=0.67 and r=0.83; P<0.001 for both), inversely related to heart rate (r=-0.38; P<0.001) and directly to venous plasma norepinephrine (r=0.28; P<0.001) and left ventricular mass index (r=0.27; P<0.001). Thus, EHT is a condition characterized by a sustained sympathetic overdrive, whose magnitude is proportional to its clinical severity. This is more clearly manifest when MSNA rather than indirect markers of adrenergic drive, such as heart rate and plasma norepinephrine, are used.