Presumptive risk factors for recurrence of neuroleptic malignant syndrome (NMS) and clinical evidence for its pathogenesis are discussed. All earlier reports describing patients who have had NMS and who were either safely restarted on neuroleptic or who developed recurrence are reviewed. The authors also present their own experiences with both outcomes. Possible risk factors for recurrent NMS are administration of high-potency neuroleptics and reintroduction of neuroleptics before the initial episode of NMS has completely resolved. Bipolar disorder and concomitant use of lithium may predispose to NMS and therefore could also heighten the risk of recurrence.