In the centennial year of the birth of Hans Selye, this review compares his classical concepts of stress with a modern approach to mechanisms of CNS arousal. Relations between the two concepts are described. Neuroanatomical, neurophysiological, and functional genomic mechanisms underlying CNS arousal are briefly reviewed. Controls over stress responses and arousal are compared to particular concepts of control system engineering. Understanding these two systems is of crucial importance because their dysregulation is associated with large numbers of disease states.