NDI occurs in 5% to 20% of patients receiving long-term lithium therapy. The associated polyuria usually resolves within 3 weeks of lithium discontinuance but can persist beyond a year. For such patients, hydrochlorothiazide and amiloride therapy has been hampered by the delayed effect and intrinsic side effects of these agents. We have described the case of a 66-year-old man with a history of bipolar disorder treated with lithium who was transferred to the intensive care unit with coma. Indomethacin therapy, at a dose of 50 mg every 8 hours, was begun and improvement of the NDI state was observed within 3 hours of lithium administration. There was complete normalization of mental status and laboratory studies after 36 hours. A complete 3-week course of indomethacin was required to keep the patient free of symptoms of NDI. We have also discussed the role of indomethacin in reversing lithium-induced NDI and reviewed pertinent prior reports in the literature.