The physiological osmolality of plasma is 288+/-5 mosmol/kgH2O when measured by freezing-point depression. The theoretical osmolarity (290 mosmol/l) calculated from composition, osmotic coefficient (0.93) and water content (0.94) is practically identical. Saline (0.9% NaCl) has an osmolarity of 308 mosmol/l and an osmolality of 286 mosmol/kgH2O (water content ca. 1.0). The osmolality in vivo is more important than that measured in vitro. A 5% dextrose solution in water (D5W) is isotonic in vitro, but the in vivo effect is that of pure water because the glucose is rapidly metabolized. Every infusion fluid should be isotonic (290+/-10 mosmol/kgH2O). Hypotonic solutions must move water from the extracellular space to the intracellular space. Typical examples are Ringer's lactate and acetate solutions (256 instead of 290 mosmol/kgH2O). The brain (central nervous system, CNS) is the critical organ: The rigidly shaped skull contains three incompressible compartments, only blood and cerebrospinal fluid (CSF) can be partially, but limitedly shifted outside the skull. The consequence of a volume load is an increasing intracranial pressure (ICP). A decrease in plasma osmolality by only 3% produces an increase in ICP of about 15 mmHg. Therefore, infusion of larger volumes of hypotonic solutions should be avoided at all costs.