The general ophthalmologist will see patients in whom neuro-ophthalmic symptoms and signs may be the presenting manifestation of an underlying systemic disease or for whom knowledge of a previous systemic diagnosis will guide appropriate subsequent evaluation and management. This symposium will review the diagnostic evaluation of neuro-ophthalmic symptoms and signs as they specifically relate to systemic disorders. Transient visual loss may be the first manifestation of giant cell arteritis and other serious systemic diseases. Evaluation for an underlying hypercoagulable state may be indicated in some patients with ocular and cerebral vascular occlusive events. Patients with an optic neuropathy may be harboring infectious, inflammatory, toxic, or nutritional disease. Cancer patients may develop visual loss due to neoplastic, paraneoplastic, or therapeutic etiologies. Ocular motility disorders affecting the extraocular muscles or one or more cranial nerves may also reflect underlying systemic disorders.