A 48-year-old woman with a history of chronic migraines, initially admitted for inpatient management of intractable migraine headaches, developed new onset abdominal pain, hypotension, and diarrhea on hospital day number ten. In our institution's headache unit, patients are treated by a multidisciplinary approach, including individualized drug therapy based on diagnosis and previous response to therapy. Given the patient's hypotension and clinical appearance, she was transferred to the intensive care unit and treated for septic shock and metabolic acidosis. A bedside colonscopy revealed diffuse ischemic colitis. Final pathology after colon resection showed widespread, transmural necrosis of the colonic wall. We review the pathophysiology of ergotamine use and its potential association with ischemic colitis.