The syndromes of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting (CSW) are two potential causes of hyponatremia is patients with disorders of the central nervous system. Distinguishing between these two causes can be challenging because there is considerable overlap in the clinical presentation. The primary distinction lies in the assessment of the effective arterial blood volume (EABV). SIADH is a volume-expanded state because of antidiuretic hormone-mediated renal water retention. CSW is characterized by a contracted EABV resulting from renal salt wasting. Making an accurate diagnosis is important because the treatment of each condition is quite different. Vigorous salt replacement is required in patients with CSW, whereas fluid restriction is the treatment of choice in patients with SIADH. Although most physicians are familiar with SIADH, they are much less familiar with CSW. This review emphasizes the need for CSW to be included in the differential diagnosis of hyponatremia in a patient with central nervous system disease. Distinguishing between these two disorders is of crucial importance because therapy indicated for one disorder but used in the other can result in negative clinical consequences.