In 1707, Valsalva reported a patient with unilateral cerebral hemorrhage associated with weakness on the contralateral side of the body, and Morgagni in De Sedibus subsequently referred to this crossed relationship of brain to body as the Valsalva doctrine. Since then, decussation of corticospinal tracts and many other neural pathways within the CNS has become so deeply embedded in neurologic thinking that exceptions may not be considered and therefore may be overlooked. Several uncommon clinical events that result in paralysis ipsilateral to brain injury highlight nuances of normal human neuroanatomy and neuropathology. More recently, exceptions to the Valsalva doctrine have been documented in 2 autosomal recessive genetic conditions: horizontal gaze palsy and progressive scoliosis and Joubert syndrome. In these syndromes, corticospinal tracts and certain other brainstem neural pathways do not decussate normally, and knowledge of the responsible genes for the first time teaches us something about the molecular mechanisms that direct the corticospinal tracts across the midline. However, we still do not understand why decussation occurs.