Human survival (on a biochemical level) depends on the body’s critical ability to regulate the osmolality and salinity of extracellular fluid. When functioning in a normal state, the osmoregulatory system stringently maintains the serum sodium in a narrow range. Alterations in the serum sodium and water balance have significant and sometimes life-threatening impact on patients—especially when they occur in conjunction with serious intracranial pathology. This chapter, including the case discussion, illustrates the conundrum of hyponatremia and high urine output states complicating neurological illness. A thorough understanding of the pathophysiology, assessment, and treatment of these conditions is essential for the timely delivery of care and optimal patient outcomes.