The historical trajectory of the discovery of the brainstem as a vital center has been rarely explored. Focusing on its tracts and neurons first, anatomists much later expanded their understanding of the brainstem with the discovery of groups of nuclear networks that affected major vital functions. Comparative anatomists (i.e., Edinger) postulated a primordial paleopallium that indirectly implied the centrality of the brainstem and a neopallidum with its differentiation and specialization up to Homo sapiens. Methods that governed the discovery of the brainstem were (1) comparative anatomy, (2) embryonic growth, (3) vivisection, (4) brain dissection, and, much later, (5) microscopy and chemical feedback loops. This historical study traces how neuroscientists of the 18th and 19th century became increasingly aware of the vital functions performed by the brainstem. The anatomists of the 20th century found the ascending reticular formation, the respiratory center, and pressor centers—all automatic and vital functions. It took centuries for this realization to open the way to use the testable brainstem centers to establish the criteria for a neurologic determination of death. The ontogenetic conclusion is that the brainstem is the ancestor of the developed human brain; the physiologic conclusion is that the brainstem is a vital center and a structural support system and conduit. When afunctional, life ends.