Although the human cerebral cortex defines the pinnacle of neuronal evolution, it remains irretrievably inoperative without input from the pervasive machinery of its phylogenetic predecessors, the monaminergic and cholinergic nuclei of the brainstem. This chapter briefly and selectively reviews the history of how this fact was discovered, updates and supplements an earlier synopsis (Daty, 1989) of various features of these rostrally projecting brainstem systems, and, from work with which I have been associated over the past couple of decades, provides a few examples reflecting operation of these brainstem processes.