Norepinephrine is the predominant endogenous sympathetic amine acting in all populations of adrenoreceptors. There is a common misperception that this amine is predominantly an α-agonist. Norepinephrine exhibits sympathetic activity over an expanding population of adrenoreceptors on the circulation (α1A and α1B, α2A, α2B and α2C, β1, β2 and β3), acting centrally on the myocardium, on the arterial (conduit) circulation and on the venous (capacitance) circulation. NE exerts its actions on target cells by binding to and activating adrenergic receptors. The target cell expression of different receptor types determines the ultimate cellular effect, and thus NE has different actions on different cell types. The signal is terminated by the removal of NE through distinct uptake mechanisms that may eventually be followed by enzymatic degradation. Part of the NE is transported by the monoamine vesicular transporter into synaptic vesicles to be further released upon stimuli, but uptake may be followed by rapid degradation to various metabolites through monoamine oxidase (MAO) or catechol-O-methyl transferase (COMT) enzymes. In neurons, MAO converts NE to the corresponding aldehyde which is then nonenzymatically further oxidized.