Impermeant molecules in the cytoplasm set the stage for an osmotic imbalance in cells. In 1960 Tosteson & Hoffman (J.Gen.Physiol, 44:169-194) demonstrated how the operation of a sodium pump, by the so-called pump-leak mechanism (PLM), can stave off an osmotic catastrophe, where water flows into the cell until it bursts. In this presentation I will explore some of the implications of the PLM in regulating cell volume under normal and pathological conditions in the brain. Here are some of the questions that I will consider: What are the roles of aquaporin channels? Can impermeant molecules drive ions out of equilibrium? What level of detail is needed in a PLM to account for cellular phenomena? Does the PLM induce activity dependent changes in neuronal size? Is deploying a sodium pump the only mechanism for ensuring volume stability? My talk also comes with an appeal to mathematicians; are there mathematical techniques that can help us better comprehend the complex interplay of ion and water fluxes in the brain?