Hyponatremia is an important and common electrolyte disorder in tumor patients and one that has been reported in association with a number of different primary diagnoses. The correct diagnosis of the pathophysiological basis for each patient is important because it significantly alters the treatment approach. In this article, we review the epidemiology and presentation of patients with hyponatremia, the pathophysiologic groups for the disorder with respect to sodium and water balance and the diagnostic measures for determining the correct pathophysiologic groups. We then present the various treatment options based on the pathophysiologic groups including a mathematical approach to the use of hypertonic saline in management. In cancer patients, hyponatremia is a serious comorbidity that requires particular attention as its treatment varies by pathophysiologic groups, and its consequences can have a deleterious effect on the patient's health.