In 1585, the renowned French royal surgeon Jacques Guillemeau published his Traité des maladies de l’oeil. The book is divided into 9 unequal sections devoted to the description of eye anatomy and ophthalmological diseases including muscle, membrane, and humor disorders; optic nerve damage; and eyelid affections. Section 3, in particular, focuses on a form of ophthalmoplegia involving progressive paralysis of extraocular muscles. Here we describe and discuss Guillemeau’s theoretical framework and practical approach to this ophthalmological disorder. To determine whether this physician was possibly influenced by the thought of antique and contemporary learned men, we reviewed some fundamental ideas on cranial nerves and their paralysis as presented by authors such as Herophilus of Chalcedon, Erasistratus of Ceos, Claudius Galen, Andreas Vesalius, and Leonhard Fuchs.