This is a case report of a patient with narcolepsy treated simultaneously with modafinil and tranylcypromine. The concurrent use of these two medications is normally contraindicated based on theoretical concerns. To our knowledge this is the first report of the combined use of these two medications in a patient for any reason. This combination of medications was particularly effective in the treatment of the patient's narcoleptic symptoms and was well tolerated, with no evidence of the potential cardiovascular side effects. Due to modafinil's lack of sympathomimetic activity and unique pharmacological profile, it may be well tolerated with monoamine oxidase inhibitor's (MAOI's) in humans with respect to hemodynamic parameters and concerns of hypertensive crisis. Further investigation would help clarify cardiovascular safety issues in using this combined therapy. We believe that with proper informed consent from the patient and careful monitoring, a combination of an MAOI and modafinil may be a viable treatment alternative in refractory cases of narcolepsy.