There is neuroanatomical, neurochemical, neurophysiologic, and behavioral preclinical evidence that suggests that the development of anxiety or fear relates, in part, to increased brain noradrenergic neuronal activity. In laboratory animals, uncontrollable stress has been shown to be associated with increases and altered regulation of brain noradrenergic function. Pharmacologic or electrical activation of noradrenergic neurons of the major brain noradrenergic nucleus, the locus ceruleus (LC), has anxiogenic effects in nonhuman primates. Elevated LC neuron firing is associated with anxiety or fear responses in freely moving cats. These observations are supported by clinical investigations that have demonstrated abnormal noradrenergic system regulation in panic disorder patients. From a neurodevelopmental perspective, these findings may be related to the natural course of panic disorder.