The psychosis, intermittent hyponatremia, and polydipsia (PIP) syndrome is a prevalent, medically serious, and difficult to treat condition in psychiatry, especially common in hospitalized chronic schizophrenic patients. In this paper, the pathophysiology and clinical manifestations of the PIP syndrome are presented as an overview, and a program of medical/pharmacologic, nursing, behavioral, and psychiatric/psychological interventions is presented and discussed. The emphasis throughout this paper is on multidisciplinary treatment approaches for patients with PIP syndrome, including medical, psychiatric, psychosocial, behavioral, and nursing contributions to the evaluation and care of these often difficult patients.