Abstract The brainstem is the lowermost, stalk-like part of the brain. Phylogenetically it is the oldest part of the human brain, similar in structure and function to the brains of reptiles and fish. The brainstem controls basic functions necessary for physiologic survival, such as heart rate, breathing, and digestion, as well as sleep-wakefulness and level of arousal in higher animals with cerebral cortex. Extensive damage to the brainstem usually results in death; lesser degrees of damage result in coma and persistent vegetative state. Focal brainstem lesions produce various combinations of impaired function of the cranial nerve nuclei, and the long ascending and descending tracts, forming the basis of brainstem syndromes, with cranial nerve-related signs providing rostral-caudal localization and long tract-related signs providing medial-lateral localization. This chapter describes basic brainstem anatomy, function, and clinical considerations related to brainstem pathology.