When humans stand or are seated, they may faint. In these positions approximately 80 % of blood volume is below the level of the heart. Veno- and vasoconstriction together with the veno-arterial reflex cannot hinder critical accumulation of blood in dependent parts of the body. Venous return needs to be supported by the muscle pump and yet, in an upright or seated position cardiac output is preload dependent even during exercise. The "plateau" of the Starling curve for the heart is reached during supine rest. Volume regulating hormones respond to the central blood volume and the reduced central blood volume of upright humans explains why the total blood volume is larger (7 % body weight) than for most animals (5 %). In the upright position, thirst and reduced diuresis enhance plasma volume. Together these observations indicate that normovolaemia may be defined for supine humans as the blood volume that does not limit cardiac output. This consideration is supported by the finding that surgical patients treated according maintaining a preload to the heart that does not limit cardiac output in so-called individualized goal-directed volume therapy demonstrate a reduced frequency of complications and even a reduced hospital stay. An explanation for that finding is that regional flow, including cerebral blood flow, seems to be restricted whenever cardiac output is limited. Accordingly, in regulation of regional flow, filling of the heart needs also to be considered and in supine humans stroke volume of the heart independent of its preload or its diastolic filling.