Recent observations from space missions indicate that weightlessness does not induce an increase in diuresis and natriuresis in astronauts. Rather, both oral fluid and sodium intake as well as renal fluid and sodium output appear reduced compared with the preflight condition. In addition, influences of reduced energy intake may be more important for total body fluid content inflight than generally assumed. Decreases in plasma volume and observations of upper body edema formation inflight indicate, in addition, an increased extravasation as a result of the headward fluid shift in weightlessness. Current simulations models of microgravity for body fluid metabolism are valid for simulations of the central fluid shift occurring in microgravity. Since weightlessness appears to decrease central venous pressure and does not induce an increased renal fluid and sodium excretion, while simulations models have opposite effects, additional models to simulate adaptation of body fluid metabolism to weightlessness might be necessary.