Background: Hyponatremia is generally defined as a serum sodium level < 135 mmol/L and is considered severe if serum sodium is < 125 mmol/L. Hyponatremia is a potentially life-threatening medical comorbidity for patients with schizophrenia. The incidence of hyponatremia in patients with schizophrenia who are taking second-generation antipsychotics (SGAs) has not been well established.; Methods: We conducted a systematic review of case reports of hyponatremia associated with the use of SGAs in patients with schizophrenia. We searched MEDLINE (from 1946 through September 2016) using the medical subject headings antipsychotic agents, hyponatremia, and water intoxication to identify reported diagnoses of hyponatremia following treatment with SGAs in patients with schizophrenia.; Results: We abstracted 12 potentially relevant case reports from 157 records. Nine case reports met the selection criteria. Three cases involved the use of aripiprazole (Abilify), 3 involved the use of risperidone (Risperdal), and the other 3 cases involved ziprasidone, olanzapine, and clozapine. Approximately equal numbers of males and females were represented, and 2 of the 9 patients were aged >= 60 years. The average patient age was 47 years, and the average time to the hyponatremia event was 17 days. The average serum sodium was 138 mmol/L at baseline, 112 mmol/L at treatment nadir, and 138 mmol/L after treatment discontinuation.; Conclusion: Hyponatremia can result from the use of SGAs in patients with schizophrenia and can be avoided with proper management of treatment. Physicians, psychiatrists, and other healthcare workers should be aware of the potential for severe hyponatremia with the use of commonly prescribed SGAs. SGA-induced hyponatremia is generally reversible after discontinuing treatment.