The description of death in medical or pathophysiological terms changed during the last century. The focus of attention shifted from the condition of the heart to the state of the brain. The current paper investigates the time period from 1866, when the effects of an increased intracranial pressure (ICP) were studied experimentally, to 1967, when the first heart transplantation was performed. Between 1894 and 1965 four neurosurgeons: Horsley in England, Cushing in USA, Wertheimer in France and Frykholm in Sweden made important contributions. Documented discussions, if ventilator treatment should be stopped in patients with a dead brain and a beating heart, began in 1959. However, already during the latter part of the 19th century it was shown that the heart could continue to beat if artificial ventilation was performed, when spontaneous respiration had ceased due to a high ICP. Furthermore, brain death was by chance implemented in clinical practice in heart surgery with cardiopulmonary bypass (CPB) some years before the expressions 'death of the nervous system' and 'brain death' were coined.