The trigemino-cardiac reflex (TCR) is defined as the sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea or gastric hypermotility during stimulation of any of the sensory branches of the trigeminal nerve. The sensory nerve endings of the trigeminal nerve send neuronal signals via the Gasserian ganglion to the sensory nucleus of the trigeminal nerve, forming the afferent pathway of the reflex arc. This afferent pathway continues along the short internuncial nerve fibers in the reticular formatio to connect with the efferent pathway in the motor nucleus of the vagus nerve. Clinically, the trigemino-cardiac reflex has been reported to occur during craniofacial surgery, balloon-compression rhizolysis of the trigeminal ganglion, and tumor resection in the cerebellopontine angle. Apart from the few clinical reports, the physiological function of this brainstem-reflex has not yet been fully explored. From experimental findings, it may be suggested that the trigemino-cardiac reflex represents an expression of a central neurogenic reflex leading to rapid cerebrovascular vasodilatation generated from excitation of oxygen-sensitive neurons in the rostral ventrolateral medulla oblongata. By this physiological response, the adjustments of the systemic and cerebral circulations are initiated to divert blood to the brain or to increase blood flow within it. As it is generally accepted that the diving reflex and ischemic tolerance appear to involve at least partially similar physiological mechanisms, the existence of such endogenous neuroprotective strategies may extend the actually known clinical appearance of the TCR and include the prevention of other potentially brain injury states as well. This may be in line with the suggestion that the TCR is a physiological, but not a pathophysiological entity.