The serum osmolality measurement has a clearly circumscribed use in clinical medicine. Comparison of the measured osmolality with the osmolality calculated from the concentrations of the major solutes in serum gives information about large deviations in the serum water content. In addition, comparison of the measured and calculated values of osmolality provides rapid screening information about the presence of foreign low-molecular-weight solutes in the blood. Taken at face value, the test cannot be used to determine whether abnormalities in tonicity homeostasis are present. A simple and direct way to assess whether tonicity is normal is to calculate the effective osmolality from the concentrations of sodium and glucose in serum. With rare exceptions, this calculation provides the information needed to make decisions about therapy.