The caudal brainstem lies at a critical nexus in the neural hierarchy that helps determine the negative feedback control of ingestion. It is the first central nervous system site that receives neural input from vagal and nonvagal visceral afferents that convey not only meal-related signals from postoral sites reflecting chemical, mechanical and nutrient properties of ingested foods, but also responses to nutrient stimulated peptides and neurotransmitters via extrinsic gut afferent receptors. In addition, the circumventricular area postrema (AP) affords the caudal brainstem access to circulating factors that are released during a meal, as well as to adiposity hormones that reflect the availability of stored nutrients. Brainstem neurons themselves express eating modulatory neuropeptides as well as their cognate receptors, raising the possibility that local ligand-receptor interactions contribute to the neural basis of eating behavior. Finally, forebrain hypothalamic projections extend to brainstem neurons that also respond to humoral and meal-related post-oral signals from peripheral gut afferents, providing critical descending influences in the negative feedback control of food intake . This article characterizes recent advances in our understanding of how peripheral, brainstem-intrinsic and descending forebrain influences may converge in the caudal brainstem to reduce food intake, with a focus on their roles in the control of meal size.