The history of pain treatment likely started in the cradle of mankind, as the experience of pain from many causes presumably had an aversive dimension comparable in its ranking to elementary sensations and motivations such as hunger, thirst, maintenance of body temperature, and sexuality-all vital for individual and genetic survival. Thus, pain certainly was among the drives to create social behavior and medicine-these functions still are inherent in pain. The period of history from 1500, as considered here, is dominated by the emergence of science. The exploration of the inside of the human body found the brain to be the seat of sensations, emotions, and behavior, and this progress included pain as well, slowly disabusing it from the magic elements and demons still inherent from early times. The rational phase of medicine began and also included new concepts of pain as first conceived by Descartes. The treatment and prevention of pain became a strong motive of medicine, with new approaches in drug treatment, physical applications such as electricity, and discoveries of psychosocial implementations. During the nineteenth century the most important breakthroughs in pain treatment included general and local anesthesia as well as analgesic drugs from morphine to anti-inflammatory agents. They succeeded in taking the terror out of the agonizing pain of surgery and dramatic courses of diseases. Today's natural extension of the medical success in controlling acute pain may be seen in the period of pain medicine aimed at understanding and preventing chronic pain.