The vagus nerve, a cranial nerve named for its “wandering” path from brainstem to bowel, is a vital conduit for brain-body communication. The vagus nerve connects the central nervous system to the digestive, cardiorespiratory, and immune systems and coordinates physiological processes to support homeostasis. This is necessary for survival since significant damage to the vagus nerve (e.g., a cervical vagotomy) can be fatal across many mammalian and avian species [1], [2], [3]. Among the tens of thousands of axons constituting the vagus nerve in mammals [4], only a minority signal from brain to viscera. These descending axons comprise the vagal efferent system and are the focus of this review. Most vagal axons transmit sensory information from viscera to the brain and are the subject of other recent reviews – e.g., [5], [6]. Also, since vagal efferent anatomy and function have been extensively reviewed elsewhere, e.g., [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], this review focuses instead on recent insights into the molecular organization of the efferent vagus gained from single-cell genomics and genetic technology.