Methylene blue has multiple indications for use, but recently it has been shown to be useful in treating refractory hypotension. Anaphylaxis results in widespread vasodilation and hypotension. Epinephrine has been described as the drug of choice in the treatment of hypotension for anaphylaxis, but the increased heart rate may be poorly tolerated by some patients. This case report describes a 79-year-old man with a history of diastolic dysfunction who was admitted for elective coronary artery bypass graft surgery. After induction of general anesthesia, symptoms of anaphylaxis developed with urticaria and decreased mean arterial pressure. The hypotension was refractory to vasoactive agents and volume repletion. Methylene blue was primed in the cardiopulmonary bypass pump and was effective in restoring hemodynamic stability. Furthermore, the patient required a decreased amount of vasoactive agents in the postoperative course. The suspected mechanism of action of methylene blue is inhibition of the enzyme nitric oxide synthase, which ultimately prevents the smooth muscle dilation that accompanies anaphylaxis. Methylene blue may be a valuable adjunct in the treatment of anaphylaxis and other causes of refractory hypotension.