Publisher Summary This chapter describes the norepinephrine (NE) system. The NE-containing neurons are located in the brainstem in the locus ceruleus (LC). The axons of these neurons conform to the usual pattern for neuromodulators of diffuse and sparse projections to all areas with little overlap. The chapter discusses the interactions of norepinephrine with transmitters such as glutamate and gamma–aminobutyric acid (GABA). NE can stimulate or inhibit neurons or can exert a biphasic effect. The postsynaptic cascades in the effects of NE with cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinases (ERKs), calcineurin, phosphatidylinositol are also explained in the chapter. The interactions between the NE system and tropins and cytokines are also discussed. NE is essential for the consolidation process of long-term memory. NE plays a role in modulating the development of neurons in various brain areas. Stress of various kinds is associated with activation of the NE system. The NE system plays a prominent role in brain mechanism subserving alertness and attention.