When thinking about neurophysiological monitoring, understanding neurophysiology means understanding why and how the central nervous system (CNS) works. This chapter will address the normal functioning of CNS as a well-organised interplay of electrical and biochemical processes. While a lot is still unknown, this synopsis of the current knowledge is crucial for understanding (a) what to monitor and (b) what the possible causes and implications of changes in the signals monitored are. This is all against the background that during perioperative care, the CNS is frequently “under the influence” of anaesthetic drugs, which not only suppress some aspects of its physiology but can also interfere with the different monitoring techniques.