Lyme disease is due to infection with a tick-borne spirochete, Borrelia burgdorferi. Risk for infection is confined to regions that contain the Ixodid tick vector. Characteristic skin, musculoskeletal, cardiac, ocular, and neurologic disorders are associated with the local, early dissemination and late stages of infection. Neurologic involvement can be seen at all stages, and involves both central and peripheral nervous system syndromes. The inability to easily culture B. burgdorferi and the lack of a reliable active infection assay have contributed to controversies in diagnosis and management. Because the vast majority of patients are seropositive, however, antibody testing is helpful to support the diagnosis of Lyme disease. With appropriate antibiotics, most patients do well. This infection provides an important model system to understand how interactions between an organism, vector, and host lead to disease. It also provides a model to study how infectious agents lead to neurologic disease.