The difficulty that nonnephrologists sometimes have with the differential diagnosis of hyponatremic patients often results from misinterpreting the significance of measured and calculated serum osmolalities, effective serum osmolalities (tonicities), and the influence of various normal (eg, serum urea nitrogen) and abnormal (eg, ethanol) solutes. Among the more commonly held misconceptions are that high serum urea or alcohol levels will, by analogy with glucose, cause hyponatremia, and that a normal (or elevated) measured serum osmolality in a hyponatremic patient excludes the possibility of hypotonicity. This article describes typical and deliberately comparative data of the serum levels of sodium, glucose, urea nitrogen, and mannitol and/or ethanol (if present); calculated and measured osmolality; effective osmolality; and the potential risk of hypotonicity-induced cerebral edema for each of 6 prototypical hyponatremic states. This provides a helpful educational tool for untangling these interrelationships and for clarifying the differences among various hyponatremic conditions.