Neurologic examination of the donkey and their hybrids (mules and hinnies) requires solid knowledge in normal neuroanatomy and neurophysiology. A systematic approach is key to preventing premature closure on differential diagnoses. A good history and collation of all clinical signs to determine one neuroanatomic area as the “common denominator” for all clinical signs should be the goal, with a multifocal or diffuse neurolocalization considered only if neuroanatomic localization to one area is impossible. This ensures that the eventual differentials list truly aligns with the patient’s clinical signs and disease process.