An historic survey is given of the gradual change of views and concepts concerning how the sympatho-adrenomedullary system is organized and operates: While it for nearly a century was considered to merely exhibit more or less generalized activation-inhibition responses, experimental studies during the last 50 years have revealed how it instead constitutes a highly sophisticated instrument for control, engaged in a variety of differentiated response patterns by which the brain controls events in major organ systems, down to include their cellular-molecular levels of organisation.