Although our knowledge of ALS manifestations in the cranial motor nerves is limited, available retrospective and prospective reports, including associated neuropathology in the cranial motor nerves, clearly indicate fruitful directions for additional biologically based studies. These data further demonstrate that the brain stem, with multiple discrete motoneuron groups, is amenable to parallel behavioral, anatomic, histochemical, and pharmacologic analyses as a means to enhance clinical diagnosis and management of ALS. Moreover, the contribution of such studies to the further understanding of the underlying mechanisms of ALS may be of even greater potential.