The trigeminocardiac reflex occurs from manipulation or stimulation of peripheral branches or the central component of the trigeminal nerve and consists of bradycardia, hypotension, apnea, and increased gastric motility. The efferent limb of the response is mediated by the vagus nerve. This 65-year-old Caucasian male suffered an episode of bradycardia progressing to transient asystole during the course of an awake-craniotomy procedure for tumor resection. The cardiac rhythm changes resolved with administration of intravenous atropine, removal of the precipitating stimulus, and application of topical anesthetic on the dura of the middle cranial fossa. The trigeminocardiac response may complicate the course of a craniotomy and may place an awake, unintubated patient at increased risk for morbidity. The reflex may be prevented by anesthetizing the dura innervated by the trigeminal nerve via injection or topical application of local anesthetic. If encountered, removal of the stimulus, airway protection, and administration of vagolytic medications are measures that need to be considered.