Pavlov’s seminal observation that sham feeding in dogs stimulates gastric acid secretion through the vagus nerve pioneered the concept of the cephalic phase of digestion. This has been subsequently extended to a wide range of mammals including humans. In the last decades, experimental evidence in rats established that the three amino acid peptide thyrotropinreleasing hormone (TRH) expressed in the brainstem plays a key role in the vagal stimulation of digestive secretory-motor function. The dorsal motor nucleus of the vagus (DMN) neurons expresses TRH receptor subtype 1 (TRH-R1) and receives input of TRH containing fibers arising from TRH synthesizing neurons in medullary raphe nuclei. The activation of TRHTRH-R1 signaling excites the firing of DMN neurons leading to the activation of vagal efferent discharges and gastric myenteric cholinergic neurons. This results in a vagally mediated and atropine-sensitive stimulation of gastric secretory and propulsive motor function, along with duodenal and pancreatic secretion. Importantly, the blockade of TRH or TRH-R1 in the brainstem inhibits the gastric acid response to sham feeding in rats. Collectively, these convergent data support the physiological relevance of medullary TRHTRH-R1 signaling as the end effector of the vagally mediated stimulation of digestive process in the cephalic phase.