Neuroleptic malignant syndrome (NMS) is a severe reaction to antipsychotic medications characterized by fever, muscle rigidity, altered mental status, and autonomic dysfunction. Here, we describe the case of a 58-year-old female who presented with altered mental status two days after open reduction and internal fixation of the hip. A rapid response team was called when the patient appeared agitated with increased respiratory demand. After being intubated and moved to the ICU, she became febrile and rigid. A preliminary diagnosis of metabolic encephalopathy of unknown origin was made. Before being transported to the ICU, the patient was given multiple haloperidol doses in addition to her continued at-home medication, paroxetine, for major depressive disorder. The differential diagnosis included a workup for NMS, serotonin syndrome, and infectious processes. Once NMS was determined as the most likely etiology, all antipsychotic and serotonergic medications were discontinued. Then dantrolene and amantadine were administered, which resulted in clinically significant improvement. This case report demonstrates the importance of early identification of and intervention for NMS.