The most adequate and successful way to understand the essence of any complex psychophysiological phenomenon, including pain, is obviously the study of its origin, its genesis, i.e., its biological background. Based on critical analysis of recent literature and our own electrophysiological, biochemical and pharmacological data we tried to overcome the difficulties and contradictions derived from the traditional reflex approach and analytical orientation in understanding the experimental investigation of pain-related problems and to determine the neurobiological background of pain and analgesia through the notion of the organism's adaptive activity. Interrelations between the notion of pain and other biological and psychological ideas, the place and functional significance of pain and endogenous analgesic mechanisms in the organization, maintenance and regulation of the organism's adaptive activity, characterization of the involvement of endogenous opioid peptides and monoamines in central processes associated with pain and analgesia, the essence and mechanisms of pain-depressing activity of the opiates are the main stages in our neurobiological consideration of the phenomenon of pain and its natural and pharmacological regulation.