Although Lyme disease affects the nervous system in many ways (collectively known as neuroborreliosis), only rarely does it present as a medical emergency. In extreme cases, it may cause (1) encephalitis, (2) a rapidly progressive peripheral neuropathy, or (3) a painful truncal radiculopathy that may be confused with a severe visceral process. Knowing when to consider this spirochetosis in the differential diagnosis requires an understanding of its true clinical spectrum, and of an appropriate diagnostic and therapeutic approach.