The spirochetal disease relapsing fever is caused by different Borrelia species. Relapsing fever is well recognized as an infection of the blood, but little is known about its predilection for the nervous system and the eyes. To investigate neurological and ocular involvement during relapsing fever, we reviewed the clinical manifestations, pathology, and treatment of relapsing fever of humans and experimental animals. The results indicate that Borrelia turicatae and Borrelia duttonii, the agents of tick-borne relapsing fever in southwestern North America and sub-Saharan Africa, respectively, cause neurological involvement as often as Borrelia burgdorferi in Lyme disease. Evidence of this is the frequent occurrence of lymphocytic meningitis and peripheral facial palsy in human disease; the identification of spirochetes in the brain and other nervous tissues of humans, animals, and arthropod vectors; and the persistence of brain infection after treatment with antibiotics that do not readily penetrate the blood-brain barrier.