Abstract: The ability of serotonin (5-HT) to facilitate or attenuate autonomic, endocrine, and behavioral responses to stressful stimuli has received much attention. The effects of 5-HT on physiologic and behavioral responses to stressful stimuli seem to depend on the brain region where it is released and the effector system it acts upon. This and the distinct morphology and topographic organization of subpopulations of serotonergic neurons have led to the hypothesis that subpopulations of serotonergic neurons are functionally distinct. Serotonin's role as a modulator of the “fight-or-flight” response is mediated in part by 5-HT release in the dorsolateral periaqueductal gray (DLPAG) and in the rostral ventrolateral medulla (RVLM), an area that contains sympathoexcitatory C1 adrenergic (A) neurons. The release of 5-HT in either region inhibits stress-induced sympathetic activity in part via actions on 5-HT1A receptors. In addition, 5-HT release in the DLPAG inhibits fight-or-flight or “Go” behaviors. The origin of endogenous 5-HT in the DLPAG and RVLM seems to be a subpopulation of serotonergic neurons within the ventrolateral PAG, a region implicated in “freezing” or “No Go” behaviors. These serotonergic neurons are located in the lateral “wings” of the dorsal raphe nucleus (DRN) a region also referred to as the ventrolateral DRN. The existence of a functional subpopulation of serotonergic neurons capable of inhibiting sympathoexcitation and fight-or-flight behavioral responses may be clinically relevant for explaining in part the efficacy of serotonergic drugs in the treatment of hypertension and panic attacks in panic disorder patients.