Methylene blue, a drug used to treat vasoplegia and methemoglobinemia, also inhibits monoamine oxidase-A. When given in combination with serotonergic medications, methylene blue can lead to serotonin excess syndrome. Given the widespread use of serotonergic medication to treat depression, anesthesia providers should be aware of this potentially lethal interaction. Patients undergoing cardiopulmonary bypass for cardiac surgery are a specific population at risk for postbypass vasoplegic shock. The use of methylene blue to treat vasoplegia in this group of patients should be weighed in light of their current medications and potential drug interactions.