Introduction Stress is a major factor in the development of many psychopathological conditions, and the dysregulation of noradrenergic neurotransmission has been implicated in a variety of stress-related neuropsychiatric diseases, such as depression, posttraumatic stress disorder (PTSD), and other anxiety disorders. Further, the brain noradrenergic system is a key regulatory target for psychotherapeutic drugs used to treat such disorders. Thus, understanding the role of brain norepinephrine (NE) in short-term coping and the response to acute stress, as well as long-term adaptation and restoration in the face of chronic or repeated stress, may be important for understanding the neurobiological processes involved in the development of or vulnerability to such pathological states and the processes involved in their effective treatment. The brain noradrenergic neurotransmitter system, originating in the locus coeruleus (LC) and other cell groups in the medulla and pons, innervates essentially the entire neuraxis, the notable exception being the neostriatum (see Chapter 1). Such a widespread and divergent innervation pattern arises from a relatively small number of cells concentrated in a few regions of the hindbrain. This system is positioned ideally to enact a global “state-change” function and influence the operating characteristics of the entire nervous system under conditions of elevated noradrenergic activity. That the system indeed operated in this manner was supported by electrophysiologic experiments in the 1980s and early 1990s, which showed the effect of NE on target neurons to be primarily modulatory in nature.