Our understanding of the pathophysiology of vasovagal syncope (VVS) has improved substantially in last 2 decades; however, the exact mechanism that leads to an episode of VVS has remained elusive. The dominant model holds that an episode of VVS has several phases. The initial phase of sympathetic stimulation occurs in response to a stressor, which may either be orthostatic, physical, or emotional. This sympathetic phase is often compensatory and results in both increased heart rate and increased myocardial contractility. The hyperdynamic contraction of the myocardium results in the activation of intramyocardial ganglionic plexi, triggering a parasympathetic counter response, and ultimately causes bradycardia, arterial vasodilatation, hypotension, cerebral hypoperfusion, and syncope. Prior studies have demonstrated that the initial sympathetic phase of VVS is characterized by an increase in circulating levels of both epinephrine and norepinephrine, with the increase in epinephrine levels proportionately higher than the increase in norepinephrine levels, especially in patients with a predominant vasodepressor component. Higher epinephrine levels may partially explain the vasodepressor component of VVS, via activation of the beta2-adrenergic receptors, contributing to peripheral arterial vasodilatation. In this issue of HeartRhythm, Benditt et al report on the age-related differences in epinephrine and norepinephrine levels during tilt-induced VVS. In a cohort of 29 patients, 12 patients were aged 40 years and older and 17 were younger than 40 years. They found that baseline epinephrine and norepinephrine levels and the baseline epinephrine/norepinephrine ratio (Epi/NE) in the 2 age groups were similar. They also found that epinephrine levels increased 12.5to 14.6-fold from the baseline to the onset of syncope, while norepinephrine levels increased to a much lower degree (1.8to 2.0-fold). However, the Epi/NE ratio was higher in younger patients at 2 minutes (1.02 vs 0.40; P 1⁄4 .11) of the upright tilt and at the onset of syncope (2.60 vs1.64; P 1⁄4 .03). On the basis of these observations, they suggest that these findings may, in part, explain why beta-blockers tended to be less effective in younger patients in randomized trials. They conclude with a call for a randomized trial addressing