The afferent vagus nerves project to diverse neural networks within the brainstem and forebrain, based on neuroanatomical, neurophysiological, and functional (fMRI) brain imaging evidence. In response to afferent vagal stimulation, multiple homeostatic visceral reflexes are elicited. Physiological stimuli and both invasive and non-invasive electrical stimulation that activate the afferent vagus elicit perceptual and behavioral responses that are of physiological and clinical significance. In the present review, we address these multiple roles of the afferent vagus under normal and pathological conditions, based on both animal and human evidence.