The use of fluid therapy attempts to optimize blood circulation by manipulating the circulating blood volume (BV). BV may be a key intermediate parameter between fluid therapy and the blood circulation, and it has been assumed that BV can be controlled by fluid therapy. In order to construct a fluid therapy protocol, firstly, we have to confirm whether BV can actually be controlled by fluid therapy. Volume kinetics studies and dilution techniques for BV measurements have enabled the actual effects of fluid management on BV to be analyzed in the presence of various pathological conditions. Various studies have shown that the effect of fluid, especially crystalloid, on BV varies considerably among individuals, and even BV values measured at a single time point vary from 40 ml·kg−1 to 110 ml·kg−1. It has become apparent that such wide variations in interindividual BV preclude the establishment of universal optimal fluid management protocols. Thus, secondly, it should be clarified how BV is controlled, and whether or not we can control it. Perioperative BV reportedly changes in a manner that is independent of the in-out fluid balance, but is related to hormonal factors. Because inflammation and some hormones control vascular permeability and the renal adjustment of solutes and fluids, such factors may readjust the BV even after interventional fluid therapy. Perioperative BV may be predominantly controlled by an internal regulatory system, regardless of whether “restrictive” or “liberal” fluid management strategies are employed. Recognizing this physiological control of BV may help us to develop individualized fluid management strategies.