Epinephrine is the prototypical stress hormone. Its stimulation of all α and β adrenergic receptors elicits short-term systolic hypertension, hyperglycemia, and other aspects of the metabolic syndrome. Acute epinephrine infusion increases cardiac output and induces insulin resistance, but removal of the adrenal medulla has no consistent effect on blood pressure. Epinephrine is the most effective endogenous agonist at the β2 receptor. Transgenic mice that cannot make epinephrine and mice that lack the β2 receptor become hypertensive during exercise, presumably owing to the absence of β2-mediated vasodilatation. Epinephrine-deficient mice also have cardiac remodeling and poor cardiac responses to stress, but do not develop resting hypertension. Mice that cannot make epinephrine have a normal metabolism on a regular 14% fat diet but become hyperglycemic and insulin resistant when they eat a high fat diet. Vigorous exercise prevents diabetes in young mice and humans that overeat. However, exercise is a less effective treatment in older type 2 human diabetics and had no effect on glucose or insulin responses in older, diabetic mice. Sensitivity of the β2 receptor falls sharply with advancing age, and adrenal epinephrine release also decreases. However, treatment of older diabetic mice with a β2 adrenergic agonist improved insulin sensitivity, indicating that β2 subsensitivity can be overcome pharmacologically. Recent studies show that over the long term, epinephrine prevents hypertension during stress and improves glucose tolerance. The hyperglycemic influence of epinephrine is short-lived. Chronic administration of epinephrine and other β2 agonists improves cellular glucose uptake and metabolism. Overall, epinephrine counteracts the metabolic syndrome.